Highly differentiated epithelial cells of the visceral layer of BOWMAN CAPSULE of the KIDNEY. They are composed of a cell body with major CELL SURFACE EXTENSIONS and secondary fingerlike extensions called pedicels. They enwrap the KIDNEY GLOMERULUS capillaries with their cell surface extensions forming a filtration structure. The pedicels of neighboring podocytes interdigitate with each other leaving between them filtration slits that are bridged by an extracellular structure impermeable to large macromolecules called the slit diaphragm, and provide the last barrier to protein loss in the KIDNEY.
A clinicopathological syndrome or diagnostic term for a type of glomerular injury that has multiple causes, primary or secondary. Clinical features include PROTEINURIA, reduced GLOMERULAR FILTRATION RATE, and EDEMA. Kidney biopsy initially indicates focal segmental glomerular consolidation (hyalinosis) or scarring which can progress to globally sclerotic glomeruli leading to eventual KIDNEY FAILURE.
The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.
A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.
The presence of proteins in the urine, an indicator of KIDNEY DISEASES.
A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Renal syndrome in human immunodeficiency virus-infected patients characterized by nephrotic syndrome, severe proteinuria, focal and segmental glomerulosclerosis with distinctive tubular and interstitial changes, enlarged kidneys, and peculiar tubuloreticular structures. The syndrome is distinct from heroin-associated nephropathy as well as other forms of kidney disease seen in HIV-infected patients.
Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.
A kidney disease with no or minimal histological glomerular changes on light microscopy and with no immune deposits. It is characterized by lipid accumulation in the epithelial cells of KIDNEY TUBULES and in the URINE. Patients usually show NEPHROTIC SYNDROME indicating the presence of PROTEINURIA with accompanying EDEMA.
KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.
PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.
The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of GLOMERULAR MESANGIAL CELLS and their EXTRACELLULAR MATRIX.
Pathological processes of the KIDNEY or its component tissues.
Membrane-bound cytoplasmic vesicles formed by invagination of phagocytized material. They fuse with lysosomes to form phagolysosomes in which the hydrolytic enzymes of the lysosome digest the phagocytized material.
Excision of kidney.
Pathological processes of the KIDNEY without inflammatory or neoplastic components. Nephrosis may be a primary disorder or secondary complication of other diseases. It is characterized by the NEPHROTIC SYNDROME indicating the presence of PROTEINURIA and HYPOALBUMINEMIA with accompanying EDEMA.
A type of glomerulonephritis that is characterized by the accumulation of immune deposits (COMPLEMENT MEMBRANE ATTACK COMPLEX) on the outer aspect of the GLOMERULAR BASEMENT MEMBRANE. It progresses from subepithelial dense deposits, to basement membrane reaction and eventual thickening of the basement membrane.
Smooth muscle-like cells adhering to the wall of the small blood vessels of the KIDNEY at the glomerulus and along the vascular pole of the glomerulus in the JUXTAGLOMERULAR APPARATUS. They are myofibroblasts with contractile and phagocytic properties. These cells and their MESANGIAL EXTRACELLULAR MATRIX constitute the GLOMERULAR MESANGIUM.
The layer of EXTRACELLULAR MATRIX that lies between the ENDOTHELIUM of the glomerular capillaries and the PODOCYTES of the inner or visceral layer of the BOWMAN CAPSULE. It is the product of these two cell types. It acts as a physical barrier and an ion-selective filter.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
A disorder of sex development characterized by UROGENITAL ABNORMALITIES; GONADAL DYSGENESIS; and WILMS TUMOR. It is caused by a mutation in the Wilms tumor suppressor gene (GENES, WILMS TUMOR) on chromosome 11.
A double-walled epithelial capsule that is the bulbous closed proximal end of the kidney tubular system. It surrounds the cluster of convoluted capillaries of KIDNEY GLOMERULUS and is continuous with the convoluted PROXIMAL KIDNEY TUBULE.
The presence of albumin in the urine, an indicator of KIDNEY DISEASES.
Hardening of the KIDNEY due to infiltration by fibrous connective tissue (FIBROSIS), usually caused by renovascular diseases or chronic HYPERTENSION. Nephrosclerosis leads to renal ISCHEMIA.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A chronic form of glomerulonephritis characterized by deposits of predominantly IMMUNOGLOBULIN A in the mesangial area (GLOMERULAR MESANGIUM). Deposits of COMPLEMENT C3 and IMMUNOGLOBULIN G are also often found. Clinical features may progress from asymptomatic HEMATURIA to END-STAGE KIDNEY DISEASE.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Isoforms encoded by the WT1 Wilms tumor suppressor gene (GENES, WILMS TUMOR) and produced by alternative splicings. They are zinc finger-containing transcription factors involved in both transactivation and repression, and are critical for normal development and function of the urogenital tract.
Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body.
A non-fibrillar collagen found in the structure of BASEMENT MEMBRANE. Collagen type IV molecules assemble to form a sheet-like network which is involved in maintaining the structural integrity of basement membranes. The predominant form of the protein is comprised of two alpha1(IV) subunits and one alpha2(IV) subunit, however, at least six different alpha subunits can be incorporated into the heterotrimer.
A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve.
Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.
A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Inflammation of the interstitial tissue of the kidney. This term is generally used for primary inflammation of KIDNEY TUBULES and/or surrounding interstitium. For primary inflammation of glomerular interstitium, see GLOMERULONEPHRITIS. Infiltration of the inflammatory cells into the interstitial compartment results in EDEMA, increased spaces between the tubules, and tubular renal dysfunction.
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.
General increase in bulk of a part or organ due to CELL ENLARGEMENT and accumulation of FLUIDS AND SECRETIONS, not due to tumor formation, nor to an increase in the number of cells (HYPERPLASIA).
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A class of enzymes that catalyzes the ATP-dependent formation of a thioester bond between itself and UBIQUITIN. It then transfers the activated ubiquitin to one of the UBIQUITIN-PROTEIN LIGASES.
A phosphatidylinositol 3-kinase subclass that includes enzymes whose specificity is limited to 1-phosphatidylinositol. Members of this class play a role in vesicular transport and in the regulation of TOR KINASES.
A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin.
Long convoluted tubules in the nephrons. They collect filtrate from blood passing through the KIDNEY GLOMERULUS and process this filtrate into URINE. Each renal tubule consists of a BOWMAN CAPSULE; PROXIMAL KIDNEY TUBULE; LOOP OF HENLE; DISTAL KIDNEY TUBULE; and KIDNEY COLLECTING DUCT leading to the central cavity of the kidney (KIDNEY PELVIS) that connects to the URETER.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The transference of a kidney from one human or animal to another.
Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.
The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.
A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.
A specialized barrier in the kidney, consisting of the fenestrated CAPILLARY ENDOTHELIUM; GLOMERULAR BASEMENT MEMBRANE; and glomerular epithelium (PODOCYTES). The barrier prevents the filtration of PLASMA PROTEINS.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance.
A ZINC-dependent membrane-bound aminopeptidase that catalyzes the N-terminal peptide cleavage of GLUTAMATE (and to a lesser extent ASPARTATE). The enzyme appears to play a role in the catabolic pathway of the RENIN-ANGIOTENSIN SYSTEM.
A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.
Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A group of differentiation surface antigens, among the first to be discovered on thymocytes and T-lymphocytes. Originally identified in the mouse, they are also found in other species including humans, and are expressed on brain neurons and other cells.
Inflammation of any part of the KIDNEY.
The functional units of the kidney, consisting of the glomerulus and the attached tubule.
Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.
A subgroup of TRP cation channels that contain 3-4 ANKYRIN REPEAT DOMAINS and a conserved C-terminal domain. Members are highly expressed in the CENTRAL NERVOUS SYSTEM. Selectivity for calcium over sodium ranges from 0.5 to 10.
A purine base and a fundamental unit of ADENINE NUCLEOTIDES.
Laboratory tests used to evaluate how well the kidneys are working through examination of blood and urine.
Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
1,4-Dihydrazinophthalazine. An antihypertensive agent with actions and uses similar to those of HYDRALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p354)
Elements of limited time intervals, contributing to particular results or situations.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.
The outer zone of the KIDNEY, beneath the capsule, consisting of KIDNEY GLOMERULUS; KIDNEY TUBULES, DISTAL; and KIDNEY TUBULES, PROXIMAL.
Established cell cultures that have the potential to propagate indefinitely.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A darkly stained mat-like EXTRACELLULAR MATRIX (ECM) that separates cell layers, such as EPITHELIUM from ENDOTHELIUM or a layer of CONNECTIVE TISSUE. The ECM layer that supports an overlying EPITHELIUM or ENDOTHELIUM is called basal lamina. Basement membrane (BM) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. BM, composed mainly of TYPE IV COLLAGEN; glycoprotein LAMININ; and PROTEOGLYCAN, provides barriers as well as channels between interacting cell layers.
Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
An abundant lysosomal-associated membrane protein that has been found to shuttle between LYSOSOMES; ENDOSOMES; and the PLASMA MEMBRANE. Loss of expression of lysosomal-associated membrane protein 2 is associated with GLYCOGEN STORAGE DISEASE TYPE IIB.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
A genus of long-legged, swift-moving felines (FELIDAE) from Africa (and formerly Asia) about the size of a small leopard.
Rats bearing mutant genes which are phenotypically expressed in the animals.
A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.
The minute vessels that connect the arterioles and venules.
Genes at loci that are involved in the development of WILMS TUMOR. Included are human WT1 at 11p13 and human WT2 (MTACR1) at 11p15.
Persistent high BLOOD PRESSURE due to KIDNEY DISEASES, such as those involving the renal parenchyma, the renal vasculature, or tumors that secrete RENIN.
Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.
A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).
A cell line derived from cultured tumor cells.
A BLOOD PRESSURE regulating system of interacting components that include RENIN; ANGIOTENSINOGEN; ANGIOTENSIN CONVERTING ENZYME; ANGIOTENSIN I; ANGIOTENSIN II; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming ANGIOTENSIN I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to ANGIOTENSIN II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal VASCULAR SMOOTH MUSCLE, leading to retention of salt and water in the KIDNEY and increased arterial blood pressure. In addition, angiotensin II stimulates the release of ALDOSTERONE from the ADRENAL CORTEX, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down BRADYKININ, a powerful vasodilator and component of the KALLIKREIN-KININ SYSTEM.
An intermediate filament protein found predominantly in smooth, skeletal, and cardiac muscle cells. Localized at the Z line. MW 50,000 to 55,000 is species dependent.
A cyclin subtype that is found abundantly in post-mitotic tissues. In contrast to the classical cyclins, its level does not fluctuate during the cell cycle.
Agents that antagonize ANGIOTENSIN II TYPE 1 RECEPTOR. Included are ANGIOTENSIN II analogs such as SARALASIN and biphenylimidazoles such as LOSARTAN. Some are used as ANTIHYPERTENSIVE AGENTS.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.
Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.
A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)
The urea concentration of the blood stated in terms of nitrogen content. Serum (plasma) urea nitrogen is approximately 12% higher than blood urea nitrogen concentration because of the greater protein content of red blood cells. Increases in blood or serum urea nitrogen are referred to as azotemia and may have prerenal, renal, or postrenal causes. (From Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
Proteolytic breakdown of the MITOCHONDRIA.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).
The process by which chemical compounds provide protection to cells against harmful agents.
An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
A nonmuscle isoform of myosin type II found predominantly in platelets, lymphocytes, neutrophils and brush border enterocytes.
Presence of blood in the urine.
Products derived from the nonenzymatic reaction of GLUCOSE and PROTEINS in vivo that exhibit a yellow-brown pigmentation and an ability to participate in protein-protein cross-linking. These substances are involved in biological processes relating to protein turnover and it is believed that their excessive accumulation contributes to the chronic complications of DIABETES MELLITUS.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A syndrome characterized by CHRONIC KIDNEY FAILURE and GONADAL DYSGENESIS in phenotypic females with karyotype of 46,XY or female individual with a normal 46,XX karyotype. It is caused by donor splice-site mutations of Wilms tumor suppressor gene (GENES, WILMS TUMOR) on chromosome 11.
Proteins that are involved in or cause CELL MOVEMENT such as the rotary structures (flagellar motor) or the structures whose movement is directed along cytoskeletal filaments (MYOSIN; KINESIN; and DYNEIN motor families).
Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., COLLAGEN; ELASTIN; FIBRONECTINS; and LAMININ).
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
Laboratory rats that have been produced from a genetically manipulated rat EGG or rat EMBRYO, MAMMALIAN. They contain genes from another species.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
Mice bearing mutant genes which are phenotypically expressed in the animals.
Inbred rats derived from Sprague-Dawley rats and used for the study of salt-dependent hypertension. Salt-sensitive and salt-resistant strains have been selectively bred to show the opposite genetically determined blood pressure responses to excess sodium chloride ingestion.
A steroid metabolite that is the 11-deoxy derivative of CORTICOSTERONE and the 21-hydroxy derivative of PROGESTERONE.
The measurement of an organ in volume, mass, or heaviness.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Macromolecular complexes formed from the association of defined protein subunits.
The return of a sign, symptom, or disease after a remission.
An angiotensin-converting enzyme inhibitor that is used to treat HYPERTENSION and HEART FAILURE.
Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.
A chemokine that is a chemoattractant for MONOCYTES and may also cause cellular activation of specific functions related to host defense. It is produced by LEUKOCYTES of both monocyte and lymphocyte lineage and by FIBROBLASTS during tissue injury. It has specificity for CCR2 RECEPTORS.
An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.
Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.
Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.
The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.
The number of CELLS of a specific kind, usually measured per unit volume or area of sample.
A rare autosomal recessive disorder resulting from the absence of CATALASE activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A major protein in the BLOOD. It is important in maintaining the colloidal osmotic pressure and transporting large organic molecules.
Water-soluble proteins found in egg whites, blood, lymph, and other tissues and fluids. They coagulate upon heating.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
An angiotensin receptor subtype that is expressed at high levels in a variety of adult tissues including the CARDIOVASCULAR SYSTEM, the KIDNEY, the ENDOCRINE SYSTEM and the NERVOUS SYSTEM. Activation of the type 1 angiotensin receptor causes VASOCONSTRICTION and sodium retention.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
Administration of high doses of pharmaceuticals over short periods of time.
The circulation of the BLOOD through the vessels of the KIDNEY.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Microscopy in which the samples are first stained immunocytochemically and then examined using an electron microscope. Immunoelectron microscopy is used extensively in diagnostic virology as part of very sensitive immunoassays.
The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.
A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.
One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACE inhibitors), orally active, that has been used in the treatment of hypertension and congestive heart failure.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.
An individual having different alleles at one or more loci regarding a specific character.
Drugs that bind to and block the activation of MINERALOCORTICOID RECEPTORS by MINERALOCORTICOIDS such as ALDOSTERONE.
An antibiotic substance derived from Penicillium stoloniferum, and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1301)
Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.
A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63)
A member of the serpin family of proteins. It inhibits both the tissue-type and urokinase-type plasminogen activators.
Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.
The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE.
A group of inherited conditions characterized initially by HEMATURIA and slowly progressing to RENAL INSUFFICIENCY. The most common form is the Alport syndrome (hereditary nephritis with HEARING LOSS) which is caused by mutations in genes for TYPE IV COLLAGEN and defective GLOMERULAR BASEMENT MEMBRANE.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A flavoprotein enzyme that catalyzes the univalent reduction of OXYGEN using NADPH as an electron donor to create SUPEROXIDE ANION. The enzyme is dependent on a variety of CYTOCHROMES. Defects in the production of superoxide ions by enzymes such as NADPH oxidase result in GRANULOMATOUS DISEASE, CHRONIC.
Sodium chloride used in foods.
Lengthy and continuous deprivation of food. (Stedman, 25th ed)
Genes that influence the PHENOTYPE only in the homozygous state.
A direct-acting vasodilator that is used as an antihypertensive agent.
Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. J Clin Invest 120:1084 ... Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin. J ... The podocyte slit diaphragm--from a thin grey line to a complex signalling hub. Nat Rev Nephrol 9:587-98. doi:10.1038/nrneph. ... Role of mTOR in podocyte function and diabetic nephropathy in humans and mice. In Invest 121:2197-209. doi:10.1172/jci44774. " ...
... a widening of the slit membranes of the podocytes, an increase in the number of mesangial cells, and an increase in mesangial ... it has a limited sensitivity as many patients with DN experience GFR loss and glomerulosclerosis without immediate elevation in ... "Autophagy in diabetic nephropathy". The Journal of Endocrinology. 224 (1): R15-30. doi:10.1530/JOE-14-0437. PMC 4238413. PMID ... renal mesangial cells and podocytes in the glomerulus.[23] Bindings of AGEs to RAGE receptors enhances production of cytosolic ...
... the podocyte, and the mesangial cell. These cells are in physical contact with one another at various locations within the ... "Autophagy in diabetic nephropathy". J Endocrinol. 224 (1): R15-30. PMC 4238413 . PMID 25349246. doi:10.1530/JOE-14-0437 ... Redirected from Diabetic glomerulosclerosis). Jump to: navigation, search Diabetic nephropathy. Two glomeruli in diabetic ... and the epithelial podocytes.[8] The GFB is responsible for the highly selective filtration of blood entering the kidney's ...
... increased appearance of podocytes and podocyte constituents in the urine is associated with glomerulosclerosis (6, 7). Together ... Δpodocyte mice. Intriguingly, autophagy deficiency dramatically sensitized podocytes toward glomerular stress. Thus, autophagy ... Glomerular podocytes exert high levels of autophagy under basal conditions. (A) In vivo analysis of autophagy using GFP-LC3 ... To confirm the ablation of autophagy in podocytes, the Atg5Δpodocyte mice were subsequently crossed to GFP-LC3 transgenic mice ...
These changes resulted ultimately in podocyte loss and late-onset glomerulosclerosis. Analysis of pathophysiological conditions ... Here we report that podocytes exhibit an unusually high level of constitutive autophagy. Podocyte-specific deletion of ... Podocytes displayed high levels of autophagy under basal conditions compared with tubular cells (. n. = 3 GFP-LC3. transgenic ... In vivo analysis of autophagy using GFP-LC3. transgenic mice (arrow indicates autophagosome within the podocyte; nidogen served ...
Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis. Autophagy 11:1130-45 ...
In both focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN), kidney injury is characterised by ... The mechanisms driving the development of extracapillary lesions in focal segmental glomerulosclerosis (FSGS) and crescentic ... Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis. Autophagy 11, 1130- ... in a model characterized with accentuated podocyte loss and glomerulosclerosis upon genetic targeting of podocyte autophagy ...
Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis. Autophagy 11: 1130- ... A) During treatment with anti-VEGF ligand, podocyte secreted VEGFA is sequestered and does not bind to either podocyte or ... resulted in severe glomerulosclerosis.96 Although mTORs role in podocytes has been more extensively studied, the mTOR ... and the foot processes of visceral epithelial cells or podocytes. In the kidney, VEGFA is expressed by both podocytes10 and ...
"Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis," Autophagy, vol. 11, ... G. R. Reddy, K. Kotlyarevska, R. F. Ransom, and R. K. Menon, "The podocyte and diabetes mellitus: is the podocyte the key to ... Z. I. Niemir, H. Stein, G. Dworacki et al., "Podocytes are the major source of IL-1α and IL-1β in human glomerulonephritides," ... c) Endothelial cells (CD31, green) and podocyte (nephrin, red) were stained in 20-week-old WT diabetic and Hmox+/− diabetic ...
i,Aim,/i,. In this study, we aimed to explore the mechanisms mediated by RIPK2 in autophagy and the relationship with ROS-NLRP3 ... RIPK2 regulates ROS-NLRP3 inflammasome signaling through autophagy and may be involved in the pathogenesis of DN. ... Autophagy was activated by high glucose at short time periods but was inhibited in the long term, demonstrating a dual role for ... of DN, by investigating the levels of RIPK2 and autophagy in glomerular mesangial cells (GMCs) stimulated with high glucose. ,i ...
Autophagy in podocytes / Zhang, L.; Livingston, M.J.; Chen, J.-K.; Dong, Z. -- PPAR- : signaling in podocyte injury / Wang, W ... Circulating soluble urokinase receptor and focal segmental glomerulosclerosis / Wei, C.; Reiser, J. -- Anti-phospholipase A2 ... Cell biology of the podocyte / Jefferson, J.A.; Shankland, S.J. -- Cell cycle and podocyte injury / Hagmann, H.H.; Shankland, S ... Triptolide protects podocytes from injury / Qin, W.; Liu, Z.-H. -- Fly : a model to study the podocyte / Na, J.; Cagan, R.L ...
The resulting loss of podocytes ultimately leads to irreversible glomerulosclerosis and kidney failure. ... autophagy, and cell cycle dysregulation. These irreversible changes can cause podocyte cell death or the detachment of ... whereas podocyte foot processes (FP) cover the outer part of the GBM. Podocyte cell bodies (CB) and major processes (MP) float ... d) Podocyte FP are defined by three membrane domains: the apical membrane domain (AMD) (blue), the basal membrane domain (BMD ...
... is essential for podocyte survival under various challenges. How podocytes maintain such a high level of autophagy, however, ... downregulated in patients with focal segmental glomerulosclerosis and mice with experimental nephropathy. Podocyte SIRPα levels ... plays a key role in promoting podocyte autophagy. Unlike other glomerular cells, podocytes strongly expressed SIRPα, which was ... and foot process fusion of podocytes (. C. ) in Sirpa-/-. mice. Foot process fusion and effacement are indicated by open and ...
Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis. Autophagy. 11:1130- ... Podocytes maintain high basal levels of autophagy independent of mtor signaling. Autophagy. 16:1932-1948. 2020. View Article : ... and increase autophagy in rat podocytes. Moreover, AGF upregulated receptor for advanced glycation end products (RAGE) ... Puerarin Attenuates Diabetic Nephropathy by Promoting Autophagy in Podocytes. Front Physiol. 11:732020. View Article : Google ...
Damage to and loss of glomerular podocytes has been identified as the culprit lesion in progressive kidney diseases. Here, we ... Keywords: end-stage renal disease; focal segmental glomerulosclerosis; hereditary nephrotic syndrome; kinase; metabolism; ... surprisingly rapid synthesis of mitochondrial proteins under steady-state conditions that was perturbed under autophagy- ... A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes Cell Rep. 2018 ...
Podocyte endoplasmic reticulum stress response, cell polarity, and autophagy play a role in maintenance of podocyte health. ... keywords = "Focal segmental glomerulosclerosis, Genetic mutation, Nephrotic syndrome, Podocyte signaling, Steroid resistant ... Podocyte endoplasmic reticulum stress response, cell polarity, and autophagy play a role in maintenance of podocyte health. ... Podocyte endoplasmic reticulum stress response, cell polarity, and autophagy play a role in maintenance of podocyte health. ...
... the importance of mammalian target of rapamycin signaling in podocytes and in essential podocyte functions, including autophagy ... Growth-dependent podocyte failure causes glomerulosclerosis. J Am Soc Nephrol 23: 1351-1363, 2012pmid:22773827. ... Emerging role of autophagy in kidney function, diseases and aging. Autophagy 8: 1009-1031, 2012pmid:22692002. ... Testosterone and 17β-estradiol have opposite effects on podocyte apoptosis that precedes glomerulosclerosis in female estrogen ...
Endothelial cell- and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis Lenoir O , Jasiek M, ... Direct action of endothelin-1 on podocytes promotes diabetic glomerulosclerosis. Lenoir O, Milon M, Virsolvy A, Hénique C, ... We will investigate mechanisms promoting podocyte aging and death. Autophagy is blocked in an age dependent manner by unknown ... In GD, podocytes may undergo detachment, apoptosis, proliferation or migration. Using podocytes from glomerular explants, we ...
Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. J Clin Invest 120:1084 ... Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin. J ... The podocyte slit diaphragm--from a thin grey line to a complex signalling hub. Nat Rev Nephrol 9:587-98. doi:10.1038/nrneph. ... Role of mTOR in podocyte function and diabetic nephropathy in humans and mice. In Invest 121:2197-209. doi:10.1172/jci44774. " ...
Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis. Autophagy 11: 1130- ... Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. J Clin Invest 120: ... Importantly, podocyte-specific knockout of autophagy related 5 in streptozotocin-treated or high-fat diet-treated diabetic mice ... Impaired podocyte autophagy exacerbates proteinuria in diabetic nephropathy. Diabetes 65: 755-767, 2016. ...
Chen, Jian-Kang (2013) PIK3C3/VPS34, the class III PtdIns 3-kinase, plays indispensable roles in the podocyte. Autophagy 9:923- ... 2013) mVps34 deletion in podocytes causes glomerulosclerosis by disrupting intracellular vesicle trafficking. J Am Soc Nephrol ... Chen, Jianchun; Chen, Jian-Kang; Harris, Raymond C (2015) EGF receptor deletion in podocytes attenuates diabetic nephropathy. J ...
Although subsequent sequencing of candidate genes chosen on the basis of podocyte biology had less success, unbiased analysis ... Although subsequent sequencing of candidate genes chosen on the basis of podocyte biology had less success, unbiased analysis ... positional cloning of the NPHS1 gene was the landmark event that established aberrant podocyte genetics as a pivotal cause of ... that monogenic inheritance of abnormalities in podocyte-specific genes disrupting filter function is only part of the story. ...
Atg (autophagy-related [gene or protein]), the abbreviation derives from the first word, autophagy, as in AuTophaGy-related. ... Mice with mutation of Atg5 or Atg7 during nephrogenesis develop mitochondrial dysfunction with mild podocyte and tubular ... dysfunction within 2 months, and focal glomerulosclerosis with kidney failure by 6 months (83). ... autophagy-related 1; Dnmt, DNA methyltransferase; Tsc1, tuberous sclerosis 1; ULK1, Unc-51-like autophagy activating kinase; ...
Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uCD80 expression in cultured podocytes. Fabry ... was studied in cultured human podocytes. Controls and Fabry patients did not differ in age, eGFR and gender. However, UPCR, ... as podocytes in primary focal and segmental glomerulosclerosis [33] and diabetes [18] and podocytes and tubular cells in IgA ... Dysregulated autophagy contributes to podocyte damage in Fabrys disease. PLoS One. 2013;8:e63506.View ArticlePubMedPubMed ...
6. Full Text Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis ... Podocytes - pathology , Phenotype , Podocytes - ultrastructure , Animals , Autophagy-Related Protein 5 , Podocytes - drug ... sclerosis , endothelial cells , autophagy , podocytes , proteinuria , diabetic nephropathy , Podocytes , Diabetic nephropathy ... Autophagy , Endothelial cells , Sclerosis , Proteinuria , apoptosis-related cysteine peptidase , LC3A , sequestosome 1 , ...
The potential renal protection of overexpressed PTEN in podocytes was partly attributed with an improvement in autophagy and ... We found that reduction of podocyte Sirt1 led to aggravated aging-induced glomerulosclerosis and albuminuria. In addition, ... We produced podocyte-specific SLK-knockout mice to address the functional role of SLK in podocytes. Mice with podocyte-specific ... loss of podocytes, and morphological evidence of podocyte injury. Thus, SLK is essential to the maintenance of podocyte ...
Our results show that cultured human podocytes or podocytes isolated from murine glomeruli bound and endocytosed Hb through the ... Therefore, we tested the hypothesis that 1) accelerated autophagy is a key contributor to VIDD; and that 2) oxidative stress is ... Recurrent and massive intravascular hemolysis induces proteinuria, glomerulosclerosis and progressive impairment of renal ... Podocytes are new cellular targets of hemoglobin-mediated renal damage.. Alfonso Rubio-Navarro, Maria Dolores Sanchez-Niño, ...
In glomeruli, the part of autophagy was shown in podocytes and endothelial cells. Podocytes are terminally differentiated cells ... and mild glomerulosclerosis (24 mo). The discrepancy between the at-a-glance high activity of autophagy in GFP-LC3 mice and the ... Thus, essential tasks of autophagy in maintenance of podocytes have been expected. GFP-LC3-expressing transgenic mice display a ... Additionally, autophagy has a secretory part for DAMPs.5 One of the best-characterized DAMPs secreted by autophagy is IL1B. ...
Moreover, podocyte-specific autophagy-deficient mice developed podocyte loss and massive proteinuria in an HFD-induced diabetic ... Glomerulosclerosis and albuminuria are characteristic histological and clinical features of diabetic nephropathy. Recent ... Impaired podocyte autophagy exacerbates proteinuria in diabetic nephropathy. Diabetes. 2016;65(3):755-67. *View Article ... Emerging role of autophagy in kidney function, diseases and aging. Autophagy. 2012;8(7):1009-31. *View Article ...
... and alters the expression and localization of podocyte associated molecules in mouse podocytes Keywords: RNA موی سر کوتاه; CCK- ... Autophagy-deficiency in hepatic progenitor cells leads to the defects of stemness and enhances susceptibility to neoplastic ... 8; Cell Counting Kit-8; FBS; fetal bovine serum; FSGS; focal segmental glomerulosclerosis; HRP; horseradish peroxidase; IFN-γ ... Keywords: RNA موی سر کوتاه; Atg; autophagy related; BafA; Bafilomycin A1; CrispR; clustered regularly interspaced short ...
podocyte` の検索結果です。- ATGC論文チェッカー|Pubmed(パブメド)の論文検 ... The results showed that paramylon attenuated renal function, glomerulosclerosis, tubulointerstitial injury, and podocyte injury ... Sulforaphane suppresses obesity-related glomerulopathy-induced damage by enhancing autophagy via Nrf2. Lu Y , Zhang Y , Lou Y ... Podocytes are a crucial component of glomeruli, the filtration units of each nephron. Podocyte injury is the initial event in ...
Podocyte deletion of Hdac1 and Hdac2 improves glomerulosclerosis and kidney failure in Tln1fl/fl Pod-rtTA TetO-Cre mice induced ... inhibiting autophagy, and reducing nephrin and podocin expression, respectively (50, 51). Therefore, further studies examining ... and podocyte-associated Hdac1 and Hdac2 genetic ablation improved proteinuria and glomerulosclerosis. Podocyte early growth ... Arrowheads depict podocyte foot process effacement. Scale bar: 1 μm. (G) Quantification of glomerulosclerosis in D. *P , 0.05 ...
Effect of aging and hypertension on renal cortex angiotensin Ⅱ expression and podocyte autophagy in rats / 中华老年医学杂志 ... including glomerulosclerosis,tubular atrophy and interstitial fibrosis were observed during aging three time points both in ... Objective To study the changes of renal cortex angiotensin Ⅱ (AngⅡ) expression and podocyte autophagy in aging rats with ... The effects and mechanisms of benazepril and losartan on glomerular podocyte autophagy in aged spontaneously hypertensive rats ...
  • Analysis of pathophysiological conditions indicated that autophagy was substantially increased in glomeruli from mice with induced proteinuria and in glomeruli from patients with acquired proteinuric diseases. (jci.org)
  • Promoting autophagy ameliorates PAN-induced proteinuria and renal pathological damage in Sirpa -/- mice. (jci.org)
  • most studies have confirmed that autophagy activity is suppressed in the kidneys of diabetic mice [ 7 , 9 , 10 ], and excessive activation of autophagy may aggravate renal cell apoptosis. (hindawi.com)
  • The rates of apoptosis and the level of reactive oxygen species (ROS) in rat podocytes were assessed by flow cytometry. (spandidos-publications.com)
  • Our results show that cultured human podocytes or podocytes isolated from murine glomeruli bound and endocytosed Hb through the megalin-cubilin receptor system, thus resulting in increased intracellular Hb catabolism, oxidative stress, activation of the intrinsic apoptosis pathway and altered podocyte morphology, with decreased expressionof the slit diaphragm proteins nephrin and synaptopodin. (readbyqxmd.com)
  • After 7 weeks of diabetes, diabetic mice lacking Vegfa in podocytes exhibited significantly greater proteinuria with profound glomerular scarring and increased apoptosis compared with control mice with diabetes or Vegfa deletion without diabetes. (diabetesjournals.org)
  • Glomerulosclerosis correlates with reduction in podocyte number that occurs through mechanisms which include apoptosis. (buildlliibrary85.fun)
  • Furthermore, TGF-β can induce podocyte apoptosis by activating the mothers against decapentaplegic homolog 9 (Smad) signaling pathway ( 9 ). (spandidos-publications.com)
  • As a nuclear transcription regulator, CHOP also controls numerous genes involved in multifaceted cellular processes including inflammation, differentiation, autophagy, and apoptosis. (frontiersin.org)
  • What about the roles mitochondria play in various key processes and pathways such as the unfolded protein response, apoptosis in normal and cancer cells, autophagy, etc. (anti-agingfirewalls.com)
  • The mechanisms driving the development of extracapillary lesions in focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN) remain poorly understood. (nature.com)
  • Necrotizing crescentic glomerulonephritis (CGN) and focal segmental glomerulosclerosis (FSGS) are life-threatening diseases leading to irreversible renal failure. (nature.com)
  • In the past 20 years, multiple genetic mutations have been identified in patients with congenital nephrotic syndrome (CNS) and both familial and sporadic focal segmental glomerulosclerosis (FSGS). (elsevier.com)
  • Characterization of the genetic basis of CNS and FSGS has led to the recognition of the importance of podocyte injury to the development of glomerulosclerosis. (elsevier.com)
  • Anabolic androgenic steroids, illicitly used by athletes and others for decades to increase muscle mass and decrease body fat, are emerging as podocyte toxins given recent descriptions of severe forms of FSGS in long-term abusers. (asnjournals.org)
  • Recent advances show that human focal segmental glomerulosclerosis (FSGS) is a primary podocytopathy caused by podocyte-specific gene mutations including NPHS1 , NPHS2 , WT-1 , LAMB2 , CD2AP , TRPC6 , ACTN4 and INF2 . (biomedcentral.com)
  • Primary (idiopathic) FSGS is due to defects inherent in the podocyte structure or function. (biomedcentral.com)
  • FSGS secondary to genetic causes, circulating permeability factor(s), hemodynamic adaptations causing glomerular hypertrophy, and direct podocyte injury also leads to indistinguishable findings of segmental glomerulosclerosis. (biomedcentral.com)
  • To comprehend how these heterogeneous injuries may lead to FSGS, it is important to understand the structure and physiologic function of the podocyte. (biomedcentral.com)
  • Mutations in structural podocyte genes cause FSGS in humans. (biomedcentral.com)
  • SRNS is the second most frequent cause of end-stage renal disease (ESRD) in childhood, and mostly associated with focal segmental glomerulosclerosis (FSGS) [ 3 ]. (chikd.org)
  • In our opinion, these features of PODXL are exactly what the two mutation studies in this gene one on autosomal dominant familial focal and segmental glomerulosclerosis (FSGS) (3) and our study on autosomal recessive juvenile parkinsonism (4) reflect. (bmj.com)
  • AC1903 suppresses severe proteinuria and prevents podocyte loss in focal segmental glomerulosclerosis (FSGS) rat model. (medchemexpress.com)
  • Podocyte-specific deletion of autophagy-related 5 (Atg5) led to a glomerulopathy in aging mice that was accompanied by an accumulation of oxidized and ubiquitinated proteins, ER stress, and proteinuria. (jci.org)
  • Further, mice lacking Atg5 in podocytes exhibited strongly increased susceptibility to models of glomerular disease. (jci.org)
  • B ) Autophagosome (arrow, left) and autolysosome (arrow, right) on electron micrographs in podocytes of wild-type mice. (jci.org)
  • C ) Podocytes displayed high levels of autophagy under basal conditions compared with tubular cells ( n = 3 GFP-LC3 transgenic mice, 30 tubules and glomeruli of each mouse were analyzed). (jci.org)
  • Unlike other glomerular cells, podocytes strongly expressed SIRPα, which was, however, downregulated in patients with focal segmental glomerulosclerosis and mice with experimental nephropathy. (jci.org)
  • Compared with WT littermates, Sirpa-deficient mice displayed greater age-related podocyte injury and proteinuria and developed more rapid and severe renal injury in various models of experimental nephropathy. (jci.org)
  • B and C ) Rapa treatment results in less pathological damage of glomerulus ( B ) and foot process fusion of podocytes ( C ) in Sirpa -/- mice. (jci.org)
  • Role of mTOR in podocyte function and diabetic nephropathy in humans and mice. (wikipedia.org)
  • Meanwhile, podocyte-specific Pkm2-knockout (KO) mice developed worse albuminuria and podocyte injury after adriamycin treatment. (bvsalud.org)
  • Furthermore, Plce1-deficient mice demonstrated diffuse mesangial expansion, podocyte loss, and focal podocyte foot process effacement. (bvsalud.org)
  • Consistent with previous findings in mice, we detected strong PLCE1 transcript expression in podocytes using single cell sequencing of human kidney tissue. (bvsalud.org)
  • In hemagglutinin-tagged Plce1 transgenic mice, Plce1 was detected in podocytes and also in glomerular arterioles using immunohistochemistry. (bvsalud.org)
  • Twelve-mo-old transplanted mice developed mesangiolysis and glomerulosclerosis with significant deterioration of kidney function. (elsevier.com)
  • To determine the role of glomerular Vegfa in the development and progression of diabetic nephropathy, we used an inducible Cre-loxP gene-targeting system that enabled genetic deletion of Vegfa selectively from glomerular podocytes of wild-type or diabetic mice. (diabetesjournals.org)
  • Both up- and downregulation of podocyte Vegfa levels during kidney development lead to glomerular disease in mice, while a reduction of glomerular VEGFA both in patients treated with VEGFA inhibitors and in adult transgenic mice with the deletion of Vegfa causes renal thrombotic microangiopathy (TMA) ( 1 , 3 - 5 ). (diabetesjournals.org)
  • In keeping with this model, overexpression of Vegfa in podocytes of transgenic mice is associated with features of diabetic nephropathy such as a thickened glomerular basement membrane and proteinuria ( 5 , 10 , 11 ). (diabetesjournals.org)
  • To determine the role of local Vegfa production in podocytes in the development and progression of diabetic nephropathy, we used the streptozotocin (STZ) model of type 1 diabetes in mice. (diabetesjournals.org)
  • In the present study a glomerulosclerosis rat model was constructed and mice were treated with different concentrations of quercetin. (spandidos-publications.com)
  • Adriamycin nephrotoxicity and subtotal nephrectomy (SNx) studies indicated that deletion of the histone methylating enzyme EZH2 from podocytes decreased H3K27me3 levels and sensitized mice to glomerular disease. (jci.org)
  • Podocyte eGFP transgenic mice were made on FVB background and crossbred to OVE26 diabetic model. (omicsdi.org)
  • The Fyn binding adapter protein ADAP has functions in kidney podocytes that were revealed in knockout mice which developed hyalinosis and glomerulosclerosis. (physiology.org)
  • Podocytes derived from knockout mice had altered morphology related to cytoskeletal changes but not integrin function. (physiology.org)
  • Human cells expressing UMOD p.Cys147Trp recapitulated the findings in UmodC147W/+ mice, and autophagy activation with mTOR inhibitors stimulated the intracellular removal of aggregated mutant UMOD. (jci.org)
  • The role of autophagy has been investigated in many types of kidney disease models, such as acute kidney injury, age-related kidney disease, DN, and polycystic kidneys [ 5 - 8 ]. (hindawi.com)
  • To explore the physiological role of autophagy in glomerular endothelial cells (GEnCs), we compared the autophagic flux among cells in the kidney under starvation. (elsevier.com)
  • Injury and loss of podocytes are leading factors of glomerular disease and renal failure. (jci.org)
  • The lesions are characterized by a loss of podocytes ( 2 , 3 ) and an accumulation of extracellular matrix ( 4 ). (spandidos-publications.com)
  • Inhibition of mTOR is most commonly associated with albuminuria and podocyte injury, but has also been linked to renal-specific TMA. (asnjournals.org)
  • We identified mammalian target of rapamycin (mTOR) as a critical regulator of PKM2 during podocyte development. (bvsalud.org)
  • Pharmacological inhibition of mTOR potently abrogated PKM2 expression and disrupted cell differentiation, indicating the existence of metabolic checkpoint that need to be satisfied in order to allow podocyte differentiation. (bvsalud.org)
  • The induction of autophagic processes in DM1 myoblasts was concomitant to p53 over-expression and inhibition of the mTOR-S6K1 pathway, causatively involved in autophagy. (buildlliibrary85.fun)
  • Treatment of rapamycin, which is a mammalian target of rapamycin (mTOR) receptor-specific inhibitor and a known autophagy activator, attenuated high-glucose-induced lipid accumulation and EMT. (meta.org)
  • Further investigations related to the effects of genetic mutations on podocytes may identify new pathways for targeting therapeutics for nephrotic syndrome. (elsevier.com)
  • SDs connect with the actin cytoskeleton to initiate signaling pathways that regulate podocyte function, namely plasticity of foot processes, mechanosensation, calcium flux, endocytosis, cell polarity, and cell survival. (frontiersin.org)
  • These processes are modulated by counterbalancing anabolic and catabolic metabolic pathways that evolved from prokaryote homologs and by hypoxia-driven and autophagy pathways that evolved in eukaryotes. (asnjournals.org)
  • Lack of metabolic analysis during podocyte development led us to explore the distribution of mitochondrial oxidative phosphorylation and glycolysis, the two major pathways of cell metabolism, in cultured podocytes during in vitro differentiation. (bvsalud.org)
  • The SD is a unique intercellular junction that connects neighboring podocyte foot processes, regulates filtration selectivity and mediates a variety of signaling pathways related to the plasticity of foot processes [ 9 ]. (chikd.org)
  • D ) Inhibition of autophagosomal degradation with chloroquine in differentiated podocytes induced a rapid accumulation of GFP-LC3-positive autophagosomes in GFP-LC3 -transgenic podocytes. (jci.org)
  • Transgenic animal studies have contributed to our understanding of podocyte pathobiology. (elsevier.com)
  • Cell biology and pathology of podocytes. (nih.gov)
  • Glomerular podocytes exert high levels of autophagy under basal conditions. (jci.org)
  • Thus, an increase in saturated FFAs is currently thought to contribute to proximal tubular cell damage and podocyte injury in diabetic nephropathy. (jmaj.jp)
  • Here, we review the evidence indicating possible mechanisms underlying cell injury caused by saturated FFAs and cell protective roles of intracellular nutrient signals and autophagy in diabetic nephropathy. (jmaj.jp)
  • Glomerulosclerosis and albuminuria are characteristic histological and clinical features of diabetic nephropathy. (jmaj.jp)
  • We are currently investigating the role of epidermal growth factor signaling in both recovery from acute kidney injury and as a mediator of progressive glomerulosclerosis and tubulointerstitial fibrosis in diabetic nephropathy. (vckd.org)
  • With intensive investigations recently, autophagy is hoped to be a potential therapeutic target to prevent or alleviate diabetic nephropathy (DN). (meta.org)
  • Podocytes in glomeruli from humans with focal segmental glomerulosclerosis or diabetic nephropathy exhibited diminished H3K27me3 and heightened UTX content. (jci.org)
  • In addition to providing possible identification of the unknown proteins involved with diabetic nephropathy, such analysis would provide novel information about early responses by podocytes in response to insulin and glucose level changes in vitro. (omicsdi.org)
  • Podocyte-specific deletion of Sirt6 exacerbates podocyte injury and proteinuria in two independent mouse models including diabetic nephropathy and adriamycin-induced nephropathy. (omicsdi.org)
  • Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin. (wikipedia.org)
  • The most consistent finding is the A3243G mutation in the MT-TL1 gene, mainly associated with focal segmental glomerulosclerosis. (cdc.gov)
  • High autophagic activity in podocytes, terminally differentiated cells that serve as main components of the kidney filtration barrier, is essential for podocyte survival under various challenges. (jci.org)
  • Prorenin receptor is essential for podocyte autophagy and survival. (mdc-berlin.de)
  • Although subsequent sequencing of candidate genes chosen on the basis of podocyte biology had less success, unbiased analysis of genetically informative kindreds and syndromic disease has led to further gene discovery. (frontiersin.org)
  • It is becoming increasingly clear both from genetic analysis and phenotypic data - including occasional response to immunosuppressive agents and post-transplant disease recurrence in Mendelian disease - that monogenic inheritance of abnormalities in podocyte-specific genes disrupting filter function is only part of the story. (frontiersin.org)
  • and that 2) oxidative stress is required to increase the expression of autophagy genes in the diaphragm. (readbyqxmd.com)
  • Protein-coding genes that affect podocyte structural stability and function can be categorized as, (1) slit diaphragm (SD)-associated, (2) actin cytoskeleton and membrane protein-encoding, (3) transcription factor and nuclear protein-encoding, (4) glomerular basement membrane (GBM), (5) mitochondrial, and (6) lysosomal, metabolic, and cytosolic protein-encoding genes ( Table 1 ). (chikd.org)
  • Herein, several SRNS-associated genes are reviewed with respect to their roles in podocyte pathobiology. (chikd.org)
  • We are interested in pursuing a microarray analysis to identify the glycosylation-related genes that are modulated in podocytes during insulin and glucose stimulation. (omicsdi.org)
  • Here we try to find the key genes change in OVE26 diabetic mouse model podocyte by microarray assay while normal FVB mouse podocyte set as control. (omicsdi.org)
  • Inhibition of autophagy by chloroquine administration significantly increased the number of autophagosomes or autolysosomes in GEnCs and proximal tubular cells, but not in podocytes, suggesting that the GEnCs exhibit substantial autophagic activity. (elsevier.com)
  • H3K27me3 was enriched at the promoter region of the Notch ligand Jag1 in podocytes, and derepression of Jag1 by EZH2 inhibition or knockdown facilitated podocyte dedifferentiation. (jci.org)
  • Conversely, inhibition of the Jumonji C domain-containing demethylases Jmjd3 and UTX increased the H3K27me3 content of podocytes and attenuated glomerular disease in adriamycin nephrotoxicity, SNx, and diabetes. (jci.org)
  • Recurrent and massive intravascular hemolysis induces proteinuria, glomerulosclerosis and progressive impairment of renal function, suggesting podocyte injury. (readbyqxmd.com)
  • Synaptopodin, a prolin-rich actin-binding protein with 2 binding sites for actin, represents a new class of actin-binding proteins which has first been localized in podocytes and a subset of telencephalic postsynaptic densities. (acris-antibodies.com)
  • Mundel P, Heid HW, Mundel TM, Krüger M, Reiser J, Kriz W. Synaptopodin: an actin-associated protein in telencephalic dendrites and renal podocytes. (acris-antibodies.com)
  • Podocin is an integral membrane protein, and acts as a binder between nephrin and podocyte actin cytoskeleton. (chikd.org)
  • TRPC6 mutations were found to cause dysregulation of the actin cytoskeleton, and result in podocyte injury, with an autosomal dominant (AD) inheritance and usually onset later in childhood [ 13 ]. (chikd.org)
  • Sirt6 has pleiotropic protective actions in podocytes including anti-inflammatory and anti-apoptotic effects, is involved in actin cytoskeleton maintenance, and promotes autophagy. (omicsdi.org)
  • Knockdown of AVIL in human podocytes reduced actin stress fibers at the cell periphery, prevented recruitment of PLCE1 to the ARP3-rich lamellipodia, blocked EGF-induced generation of diacylglycerol (DAG) by PLCE1, and attenuated the podocyte migration rate (PMR). (jci.org)
  • The GFB comprises three layers: fenestrated endothelium, glomerular basement membrane (GBM) and podocytes, specialized terminally differentiated epithelial cells connected by slit diaphragms (SD), unique intercellular junctions interposed between interdigitating foot processes ( 1 ). (frontiersin.org)
  • Podocytes are a major GFB component, and are considered to be highly specialized and terminally-differentiated with limited regenerative capacity. (chikd.org)
  • Podocytes, a type of highly specialized epithelial cells, require substantial levels of energy to maintain glomerular integrity and function, but little is known on the regulation of podocytes' energetics. (bvsalud.org)
  • Glomerular visceral epithelial cells, known as podocytes, are a major source of VEGFA in the kidney ( 2 ). (diabetesjournals.org)
  • Podocytes, also known as glomerular visceral epithelial cells, are located outside the glomerular basement membrane. (bioscientifica.com)
  • RIPK2 regulates ROS-NLRP3 inflammasome signaling through autophagy and may be involved in the pathogenesis of DN. (hindawi.com)
  • MiR-27b regulates podocyte survival through targeting adenosine receptor 2B in podocytes from non-human primate. (nih.gov)
  • Transient receptor potential channel 6 (encoded by TRPC6 ) binds to podocin, and regulates the calcium influx into the podocytes. (chikd.org)
  • Podocyte injury leads to foot process effacement, and is associated with urinary protein leakage, renal function deterioration, and progression to ESRD [ 8 ]. (chikd.org)
  • Sirt6 also reduces urokinase plasminogen activator receptor expression, which is a key factor for podocyte foot process effacement and proteinuria. (omicsdi.org)
  • Recently, autophagy has been identified as a major pathway that delivers damaged proteins and organelles to lysosomes in order to maintain cellular homeostasis. (jci.org)
  • Although we attempt to be comprehensive, our goal is not to capture every membrane-mediated pathway but rather to emphasize that this approach may be fruitful in understanding the podocyte and its unique properties. (nih.gov)
  • Sustained elevation of Ca 2+ influx into podocytes may represent a common pathway driving these changes ( Lavin and Winn, 2011 ). (aspetjournals.org)
  • TRPC6 channels are not the only possible pathway for Ca 2+ influx into podocytes. (aspetjournals.org)
  • Autophagy is a highly conserved 'self-eating' pathway by which cells degrade and recycle macromolecules and organelles. (meta.org)
  • Emerging body of evidence suggests that targeting the autophagic pathway to activate and restore autophagy activity may be renoprotective. (meta.org)
  • Bussolati B, Deregibus MC, Fonsato V, Doublier S, Spatola T et al (2005) Statins prevent oxidized LDL-induced injury of glomerular podocytes by activating the phosphatidylinositol 3-kinase/AKT-signaling pathway. (springer.com)
  • The transforming growth factor‑β (TGF‑β) signaling pathway is an important regulatory pathway in renal fibrosis and is abnormally activated in glomerulosclerosis. (spandidos-publications.com)
  • It was demonstrated that quercetin significantly improved physiological indices and altered the expression levels of TGF‑β signaling pathway‑associated proteins in rats with glomerulosclerosis. (spandidos-publications.com)
  • In conclusion, quercetin can regulate the TGF‑β signaling pathway and reduce the progression of glomerulosclerosis. (spandidos-publications.com)
  • Glomerulosclerosis (GS) is the final pathway leading to the loss of renal function caused by a phenotypic transition of mesangial cells and an increase in extracellular matrix formation ( 1 ). (spandidos-publications.com)
  • These data suggest that endothelial autophagy protects glomeruli from oxidative stress and maintains the integrity of glomerular capillaries. (elsevier.com)
  • Autophagy serves as an essential mechanism to maintain homeostasis of glomeruli and tubules, and plays important roles in human health and diseases. (meta.org)
  • This ended any uncertainty whether genetic mutation plays a significant role in hereditary nephrotic syndromes (NS) and confirmed podocytes as critical players in regulating glomerular protein filtration. (frontiersin.org)
  • Glomerular endothelial cells (E) lining the capillary lumen (CL) and mesangial cells (M) are located on the blood side of the GBM, whereas podocyte foot processes (FP) cover the outer part of the GBM. (nih.gov)
  • A series of small foot processes extend from the major processes of podocytes and attach to the external face of the basement membrane of the glomerular capillary. (aspetjournals.org)
  • Structural alterations in podocyte foot processes occur in many glomerular diseases, leading to loss or displacement of slit diaphragms ( Shirato, 2002 ). (aspetjournals.org)
  • It is clear that numerous podocyte gene products are required to construct the podocyte body and foot processes (FPs). (biomedcentral.com)
  • In this study, we aimed to explore the mechanisms mediated by RIPK2 in autophagy and the relationship with ROS-NLRP3 of DN, by investigating the levels of RIPK2 and autophagy in glomerular mesangial cells (GMCs) stimulated with high glucose. (hindawi.com)
  • [8] Concurrently, there are changes within the glomerulus itself: these include a thickening of the basement membrane , a widening of the slit membranes of the podocytes , an increase in the number of mesangial cells, and an increase in mesangial matrix. (wikipedia.org)
  • The pathophysiology of the glomerulus in DN can best be understood by considering the three involved cells as a unit: the endothelial cell , the podocyte , and the mesangial cell . (wikipedia.org)
  • We postulate that constitutive and induced autophagy is a major protective mechanism against podocyte aging and glomerular injury, representing a putative target to ameliorate human glomerular disease and aging-related loss of renal function. (jci.org)
  • Furthermore, podocyte injury is important in the development of DN in both type 1 and type 2 diabetes mellitus (DM) [ 4 - 6 ]. (hindawi.com)
  • Podocyte plasma membrane proteins and a canonical pattern of injury. (nih.gov)
  • Podocyte SIRPα levels were inversely correlated with the severity of podocyte injury and proteinuria but positively with autophagy. (jci.org)
  • Thus, AGF induces rat podocyte injury by aggravating oxidative stress, promoting the inflammatory response, and regulating ROS‑mediated NF‑κB/RAGE activation. (spandidos-publications.com)
  • The results showed that paramylon attenuated renal function, glomerulosclerosis, tubulointerstitial injury, and podocyte injury in the CKD rat model. (atgcchecker.com)
  • In this review, we examine current advances in our understanding of the roles of autophagy in diabetic kidney injury, focusing on studies in renal cells in culture, human kidney tissues, and experimental animal models of diabetes. (meta.org)
  • 6. Telomerase, Autophagy and Acute Kidney Injury. (vckd.org)
  • Podocyte injury is a major determinant in proteinuric kidney disease and identification of potential therapeutic targets for preventing podocyte injury has clinical importance. (omicsdi.org)
  • Here, we show that histone deacetylase Sirt6 protects against podocyte injury through epigenetic regulation of Notch signaling. (omicsdi.org)
  • Podocyte injury is a critical factor in the development and progression of DN. (bioscientifica.com)
  • Persistent proteinuria, which indicates podocyte injury, is an important clinical feature of DN. (bioscientifica.com)
  • The podocyte slit diaphragm--from a thin grey line to a complex signalling hub. (wikipedia.org)
  • The results from this analysis will be utilized to focus our research with regard to glycosylation of the proteins in the podocyte slit diaphragm. (omicsdi.org)
  • Rearrangements of the cytoskeleton and cell contacts induce process formation during differentiation of conditionally immortalized mouse podocyte cell lines. (acris-antibodies.com)
  • Autophagy clears damaged proteins and organelles to maintain cellular homeostasis [ 4 ]. (hindawi.com)
  • The function of podocytes is based on their intricate cell architecture. (nih.gov)
  • Mundel P, Kriz W. Structure and function of podocytes: an update. (acris-antibodies.com)
  • Shown is an (incomplete) list of membrane proteins that have been implicated in the regulation of podocyte function in health and disease. (nih.gov)
  • Phospholipase C epsilon 1 (encoded by PLCE1 ) is expressed in the developing kidney, and affects cell adhesion by interacting with podocyte cell junction proteins. (chikd.org)
  • Recent insights have defined the central role of the podocyte as both the regulator of glomerular development as well as the determinant of progression to glomerulosclerosis and renal failure. (uni-freiburg.de)
  • In addition, we found a shift of predominant energy source from anaerobic glycolysis in immature podocyte to oxidative phosphorylation during the differentiation process. (bvsalud.org)
  • Pkm2-knockdown podocytes showed dramatic reduction of energy metabolism, resulting in defects of cell differentiation. (bvsalud.org)
  • Mundel P, Reiser J, Kriz W. Phenotypic conversion and differentiation of human and rat podocytes in vitro. (acris-antibodies.com)
  • Exposing cells to NMDA for 24 h reduced total and cell surface expression of the podocyte markers nephrin and podocin, but there was no loss of cells. (aspetjournals.org)
  • Using podocytes from glomerular explants, we will address the effects of GPCR agonists on in vitro models of each of these changes. (uni-freiburg.de)
  • VEGFA is released from podocytes and binds to its receptor (VEGFR2) on glomerular endothelial cells. (asnjournals.org)
  • autophagy and its potential upregulator receptor-interacting protein kinase 2 (RIPK2) are associated with ROS, which play a potential role in regulating NLRP3, and may be involved in inflammation in DN. (hindawi.com)
  • Defective extracellular matrix synthesis by the podocyte can lead to loss of normal glomerular filtration. (biomedcentral.com)
  • Since the lipid nephrotoxicity hypothesis was proposed in 1982, increasing evidence has supported the hypothesis that lipid abnormalities contributed to the progression of glomerulosclerosis. (springer.com)
  • The present study evaluated the mitochondrial fission of podocytes in patients with DN. (bioscientifica.com)
  • As an integral member of the filtration barrier in the kidney glomerulus, the podocyte is in a unique geographical position: It is exposed to chemical signals from the urinary space (Bowman's capsule), it receives and transmits chemical and mechanical signals to/from the glomerular basement membrane upon which it elaborates, and it receives chemical and mechanical signals from the vascular space with which it also communicates. (nih.gov)
  • c ) Transmission electron microscopy image of the filtration barrier consisting of fenestrated endothelium, GBM, and podocyte FP with the SD covering the filtration slits. (nih.gov)
  • Although damage to any of the three layers can result in significant proteinuria and kidney disease ( 3 ), podocytes are considered pivotal for maintaining barrier integrity. (frontiersin.org)
  • Identifying a monogenic cause for SRNS may lead to a better understanding of podocyte structure and function in the glomerular filtration barrier. (chikd.org)
  • Podocytes are cells of the visceral epithelium in the kidneys and form a crucial component of the glomerular filtration barrier, contributing to size selectivity and maintaining a massive filtration surface. (omicsdi.org)
  • Podocytes form filtration barrier through foot process around glomerualar basement membrane and selectively permit permeability of molecular smaller than albumin. (omicsdi.org)
  • Although size is the primary determinant of molecular filterability, recent detection of mutations in the main component of the podocyte glycocalyx, podocalyxin, in familial NS ( 2 ) supports additional charge selection through electrostatic repulsion. (frontiersin.org)
  • Kim KA, Shin YJ, Akram M, Kim ES, Choi KW, Suh H, Lee CH and Bae ON: High glucose condition induces autophagy in endothelial progenitor cells contributing to angiogenic impairment. (spandidos-publications.com)
  • Impairment of autophagy is implicated in the pathogenesis of DN. (meta.org)
  • Our findings thus demonstrate a critical protective role of SIRPα in podocyte survival via maintenance of autophagic activity. (jci.org)
  • Based on evidences that autophagy and lipid metabolism are closely related, we investigated autophagy under diabetic conditions and how it contributed in the lipotoxicity and EMT. (meta.org)
  • Podocyte endoplasmic reticulum stress response, cell polarity, and autophagy play a role in maintenance of podocyte health. (elsevier.com)
  • Apolipoprotein L1-Specific Antibodies Detect Endogenous APOL1 inside the Endoplasmic Reticulum and on the Plasma Membrane of Podocytes. (atgcchecker.com)
  • Cybulsky AV (2017) Endoplasmic reticulum stress, the unfolded protein response and autophagy in kidney diseases. (springer.com)