Podocytes
Kidney Glomerulus
Puromycin Aminonucleoside
Glomerulosclerosis, Focal Segmental
Nephrosis
Bowman Capsule
Glomerular Basement Membrane
AIDS-Associated Nephropathy
Glomerular Filtration Barrier
WT1 Proteins
Nephrotic Syndrome
Kidney
Membrane Proteins
Diabetic Nephropathies
Glomerulonephritis
Cyclin I
Glomerulonephritis, Membranous
Cells, Cultured
Nephrosis, Lipoid
Denys-Drash Syndrome
Sialoglycoproteins
Mesangial Cells
Mice, Transgenic
Cell Line, Transformed
Glomerular Mesangium
Microfilament Proteins
Zonula Occludens-1 Protein
Actinin
Microscopy, Immunoelectron
Actins
TRPC Cation Channels
Epithelial Cells
RNA, Messenger
Glomerulonephritis, IGA
NF-kappaB regulates Fas-mediated apoptosis in HIV-associated nephropathy. (1/918)
Renal parenchymal injury in HIV-associated nephropathy (HIVAN) is characterized by epithelial proliferation, dedifferentiation, and apoptosis along the entire length of the nephron. Although apoptotic cell death in HIVAN has been well documented, the mechanism for HIV-induced apoptosis is poorly understood. Whether the epithelial apoptosis in HIVAN is mediated by NF-kappaB-activated Fas ligand expression was investigated here. In human HIVAN and HIV-1 transgenic mouse kidney specimens, the expression of Fas receptor and ligand proteins were markedly upregulated on epithelium in diseased glomerular and tubulointerstitial compartments when compared with normal. Podocyte cell lines that were derived from HIV-1 transgenic mice showed a similar upregulation of Fas receptor expression and de novo expression of Fas ligand by semiquantitative reverse transcription-PCR and Western blotting. In cultured podocytes, cross-linking of the Fas receptor to mimic ligand binding induced caspase 8 activity and apoptosis in both normal and HIVAN podocytes. Because constitutive NF-kappaB activity has been demonstrated in HIVAN epithelia, evidence for transcriptional control of the Fas ligand expression by NF-kappaB was sought. With the use of cultured podocytes, expression of a Fas ligand promoter reporter plasmid was higher in HIVAN podocytes, indicating increased transcriptional activity. In addition, chromatin immunoprecipitation assays were performed to demonstrate that p65-containing (RelA) complexes bound the Fas ligand promoter and that suppression of activated NF-kappaB with a peptide inhibitor could reduce the expression of Fas ligand mRNA in HIVAN podocytes. These results suggest that NF-kappaB may regulate Fas-mediated apoptosis in HIVAN by controlling the expression of Fas ligand in renal epithelium. (+info)Dexamethasone prevents podocyte apoptosis induced by puromycin aminonucleoside: role of p53 and Bcl-2-related family proteins. (2/918)
Nephrotic-range proteinuria is due to glomerular diseases characterized by podocyte injury. Glucocorticoids are the standard of care for most forms of nephrotic syndrome. However, the precise mechanisms underlying the beneficial effects of glucocorticoids on podocytes, beyond its general immunosuppressive and anti-inflammatory effects, are still unknown. This study tested the hypothesis that the synthetic glucocorticoid dexamethasone directly reduces podocyte apoptosis. Growth-restricted immortalized mouse podocytes in culture were exposed to puromycin aminonucleoside (PA) to induce apoptosis. Our results showed that dexamethasone significantly reduced PA-induced apoptosis by 2.81-fold. Dexamethasone also rescued podocyte viability when exposed to PA. PA-induced apoptosis was associated with increased p53 expression, which was completely blocked by dexamethasone. Furthermore, the inhibition of p53 by the p53 inhibitor pifithrin-alpha protected against PA-induced apoptosis. Dexamethasone also lowered the increase in the proapoptotic Bax, which was increased by PA, and increased expression of the antiapoptotic Bcl-xL protein. Moreover, the decrease in p53 by dexamethasone was associated with increased Bcl-xL levels. Podocyte apoptosis induced by PA was caspase-3 independent but was associated with the translocation of apoptosis-inducing factor (AIF) from the cytoplasm to nuclei. AIF translocation was inhibited by dexamethasone. These results show that PA-induced podocyte apoptosis is p53 dependent and associated with changes in Bcl-2-related proteins and AIF translocation. The protective effects of dexamethasone on PA-induced apoptosis were associated with decreasing p53, increasing Bcl-xL, and inhibition of AIF translocation. These novel findings provide new insights into the beneficial effects of corticosteroids on podocytes directly, independent of its immunosuppressive effects. (+info)Permanent genetic tagging of podocytes: fate of injured podocytes in a mouse model of glomerular sclerosis. (3/918)
Injured podocytes lose differentiation markers. Therefore, the true identity of severely injured podocytes remains unverified. A transgenic mouse model equipped with a podocyte-selective injury induction system was established. After induction of podocyte injury, mice rapidly developed glomerulosclerosis, with downregulation of podocyte marker proteins. Proliferating epithelial cells accumulated within Bowman's space, as seen in collapsing glomerulosclerosis. In this study, the fate of injured podocytes was pursued. Utilizing Cre-loxP recombination, the podocyte lineage was genetically labeled with lacZ in an irreversible manner. After podocyte injury, the number of lacZ-labeled cells, which were often negative for synaptopodin, progressively declined, correlating with glomerular damage. Parietal epithelial cells, but not lacZ-labeled podocytes, avidly proliferated. The cells proliferating within Bowman's capsule and, occasionally, on the outer surface of the glomerular basement membrane were lacZ-negative. Thus, when podocytes are severely injured, proliferating parietal epithelial cells migrate onto the visceral site, thereby mimicking proliferating podocytes. (+info)Role of p38 mitogen-activated protein kinase activation in podocyte injury and proteinuria in experimental nephrotic syndrome. (4/918)
Podocytes play an important role in maintaining normal glomerular function and structure, and podocyte injury leads to proteinuria and glomerulosclerosis. The family of mitogen-activated protein kinases (MAPK; extracellular signal-regulated kinase [ERK], c-Jun N-terminal kinase, and p38) may be implicated in the progression of various glomerulopathies, but the role of MAPK in podocyte injury remains elusive. This study examined phosphorylation of p38 MAPK in clinical glomerulopathies with podocyte injury, as well as in rat puromycin aminonucleoside (PAN) nephropathy and mouse adriamycin (ADR) nephropathy. The effect of treatment with FR167653, an inhibitor of p38 MAPK, was also investigated in rodent models. In human podocyte injury diseases, the increased phosphorylation of p38 MAPK was observed at podocytes. In PAN and ADR nephropathy, the phosphorylation of p38 MAPK and ERK was marked but transient, preceding overt proteinuria. Pretreatment with FR167653 (day -2 to day 14, subcutaneously) to PAN or ADR nephropathy completely inhibited p38 MAPK activation and attenuated ERK phosphorylation, with complete suppression of proteinuria. Electron microscopy and immunohistochemistry for nephrin and connexin43 revealed that podocyte injury was markedly ameliorated by FR167653. Furthermore, early treatment with FR167653 effectively prevented glomerulosclerosis and renal dysfunction in the chronic phase of ADR nephropathy. In cultured podocytes, PAN or oxidative stress induced the phosphorylation of p38 MAPK along with actin reorganization, and FR167653 inhibited such changes. These findings indicate that the activation of MAPK is necessary for podocyte injury, suggesting that p38 MAPK and, possibly, ERK should become a potential target for therapeutic intervention in proteinuric glomerulopathies. (+info)Actin cytoskeleton regulates extracellular matrix-dependent survival signals in glomerular epithelial cells. (5/918)
Adhesion of rat glomerular epithelial cells (GEC) to collagen activates focal adhesion kinase (FAK) and the Ras-extracellular signal-regulated kinase (ERK) pathway and supports survival (prevents apoptosis). The present study addresses the relationship between actin organization and the survival phenotype. Parental GEC (adherent to collagen) and GEC stably transfected with constitutively active mutants of mitogen-activated protein kinase kinase (R4F-MEK) or FAK (CD2-FAK) (on plastic) showed ERK activation, low levels of apoptosis, and a cortical distribution of F-actin. Parental GEC adherent to plastic showed increased apoptosis, disorganization of cortical F-actin, and formation of prominent stress fibers. Assembly of cortical F-actin was, at least in part, mediated via ERK. However, disruption of the actin cytoskeleton with cytochalasin D or latrunculin B in parental GEC (on collagen) and in GEC that express R4F-MEK or CD2-FAK (on plastic) decreased ERK activation and increased apoptosis. Expression of a constitutively active RhoA (L(63)RhoA) induced assembly of cortical F-actin, promoted ERK activation, and supplanted the requirement of collagen for survival. Adhesion of GEC to collagen increased phosphatidylinositol-4,5-bisphosphate (PIP(2)). Downregulation or sequestration of PIP(2) by transfection with an inositol 5'-phosphatase or the plextrin-homology domain of phospholipase C-delta1 decreased F-actin content and survival. Moreover, overexpression of wild-type or K256E mutant alpha-actinin-4 with increased affinity for F-actin increased apoptosis. These results demonstrate a reciprocal relationship between collagen-induced cortical F-actin assembly and collagen-dependent survival signaling, including ERK activation. Appropriate remodeling of the actin cytoskeleton may be necessary for facilitating survival, as both disassembly and excessive crosslinking affect survival adversely. (+info)Organization of the pronephric filtration apparatus in zebrafish requires Nephrin, Podocin and the FERM domain protein Mosaic eyes. (6/918)
Podocytes are specialized cells of the kidney that form the blood filtration barrier in the kidney glomerulus. The barrier function of podocytes depends upon the development of specialized cell-cell adhesion complexes called slit-diaphragms that form between podocyte foot processes surrounding glomerular blood vessels. Failure of the slit-diaphragm to form results in leakage of high molecular weight proteins into the blood filtrate and urine, a condition called proteinuria. In this work, we test whether the zebrafish pronephros can be used as an assay system for the development of glomerular function with the goal of identifying novel components of the slit-diaphragm. We first characterized the function of the zebrafish homolog of Nephrin, the disease gene associated with the congenital nephritic syndrome of the Finnish type, and Podocin, the gene mutated in autosomal recessive steroid-resistant nephrotic syndrome. Zebrafish nephrin and podocin were specifically expressed in pronephric podocytes and required for the development of pronephric podocyte cell structure. Ultrastructurally, disruption of nephrin or podocin expression resulted in a loss of slit-diaphragms at 72 and 96 h post-fertilization and failure to form normal podocyte foot processes. We also find that expression of the band 4.1/FERM domain gene mosaic eyes in podocytes is required for proper formation of slit-diaphragm cell-cell junctions. A functional assay of glomerular filtration barrier revealed that absence of normal nephrin, podocin or mosaic eyes expression results in loss of glomerular filtration discrimination and aberrant passage of high molecular weight substances into the glomerular filtrate. (+info)Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. (7/918)
Glomerular injury and proteinuria in diabetes (types 1 and 2) and IgA nephropathy is related to the degree of podocyte depletion in humans. For determining the causal relationship between podocyte depletion and glomerulosclerosis, a transgenic rat strain in which the human diphtheria toxin receptor is specifically expressed in podocytes was developed. The rodent homologue does not act as a diphtheria toxin (DT) receptor, thereby making rodents resistant to DT. Injection of DT into transgenic rats but not wild-type rats resulted in dose-dependent podocyte depletion from glomeruli. Three stages of glomerular injury caused by podocyte depletion were identified: Stage 1, 0 to 20% depletion showed mesangial expansion, transient proteinuria and normal renal function; stage 2, 21 to 40% depletion showed mesangial expansion, capsular adhesions (synechiae), focal segmental glomerulosclerosis, mild persistent proteinuria, and normal renal function; and stage 3, >40% podocyte depletion showed segmental to global glomerulosclerosis with sustained high-grade proteinuria and reduced renal function. These pathophysiologic consequences of podocyte depletion parallel similar degrees of podocyte depletion, glomerulosclerosis, and proteinuria seen in diabetic glomerulosclerosis. This model system provides strong support for the concept that podocyte depletion could be a major mechanism driving glomerulosclerosis and progressive loss of renal function in human glomerular diseases. (+info)Altered expression of junctional adhesion molecule 4 in injured podocytes. (8/918)
Recent investigations have revealed the importance of glomerular podocytes with its diaphragm as the major filtration barrier. Junctional adhesion molecule 4 (JAM4) has been identified as a protein that interacts with membrane-associated guanyl kinase inverted (MAGI)-1 and is reported to be expressed on podocytes. To elucidate the role of JAM4 on podocytes, we examined the expression of JAM4 and MAGI-1 in normal and two different proteinuric rat models: puromycin aminonucleoside (PAN) nephropathy and anti-nephrin antibody-induced (ANA) nephropathy, one model with and one without effacement of podocyte foot processes. JAM4 was detected by immunomicroscopy at the apical membrane of normal podocytes. JAM4 immunostaining was focally increased in the podocytes in PAN nephropathy but not in ANA nephropathy. In proteinuric podocytes, the expression of JAM4 was distinct from that of MAGI-1 or other slit diaphragm molecules such as nephrin and ZO-1. Close colocalization of JAM4 and ezrin was maintained in PAN nephropathy. By immunoelectron microscopy, the signals for JAM4 were detected at the free apical membrane of the podocytes with effaced foot processes. Studies with selective detergent extract revealed that the subcellular localization of JAM4 was altered in PAN nephropathy. Thus the altered expression of JAM4 appears to be associated with morphological changes in podocytes and can be a useful marker of injured podocytes. JAM4 may have a different role at the apical membrane besides the role as a junctional molecule and is likely associated with the unique structure of this epithelium. (+info)Podocytes are specialized cells that make up the visceral epithelial layer of the glomerular basement membrane in the kidney. They have long, interdigitating foot processes that wrap around the capillaries of the glomerulus and play a crucial role in maintaining the filtration barrier of the kidney. The slit diaphragms between the foot processes allow for the passage of small molecules while retaining larger proteins in the bloodstream. Podocytes also contribute to the maintenance and regulation of the glomerular filtration rate, making them essential for normal renal function. Damage or loss of podocytes can lead to proteinuria and kidney disease.
A kidney glomerulus is a functional unit in the nephron of the kidney. It is a tuft of capillaries enclosed within a structure called Bowman's capsule, which filters waste and excess fluids from the blood. The glomerulus receives blood from an afferent arteriole and drains into an efferent arteriole.
The process of filtration in the glomerulus is called ultrafiltration, where the pressure within the glomerular capillaries drives plasma fluid and small molecules (such as ions, glucose, amino acids, and waste products) through the filtration membrane into the Bowman's space. Larger molecules, like proteins and blood cells, are retained in the blood due to their larger size. The filtrate then continues down the nephron for further processing, eventually forming urine.
Puromycin aminonucleoside is not a medical condition, but rather a laboratory reagent used in research. It is a synthetic antibiotic and analogue of the amino acid tyrosine, which specifically inhibits protein synthesis in eukaryotic cells by interacting with the peptidyl transferase center of the 60S ribosomal subunit. This compound has been widely used as a tool to study various cellular processes, including programmed cell death (apoptosis), autophagy, and lysosome biogenesis. Prolonged exposure to puromycin aminonucleoside can induce cytopathic effects, such as vacuolization and detachment of cells, which are often used as markers for its effectiveness in inhibiting protein synthesis.
Focal segmental glomerulosclerosis (FSGS) is a pattern of kidney injury that involves scarring or sclerosis in some (segmental) areas of some (focal) glomeruli. Glomeruli are the tiny blood vessel clusters within the kidneys that filter waste and excess fluids from the blood.
In FSGS, the scarring occurs due to damage to the glomerular basement membrane, which can be caused by various factors such as genetic mutations, viral infections, or immune system disorders. The damage leads to the accumulation of extracellular matrix proteins and the formation of scar tissue, impairing the kidney's ability to filter blood effectively.
FSGS is characterized by proteinuria (protein in the urine), hematuria (blood in the urine), hypertension (high blood pressure), and declining kidney function, which can lead to end-stage renal disease if left untreated. The focal and segmental nature of the scarring means that not all glomeruli are affected, and only some areas of each affected glomerulus are damaged, making FSGS a highly variable condition with different clinical presentations and outcomes.
Nephrosis is an older term that was used to describe a group of kidney diseases, primarily characterized by the damage and loss of function in the glomeruli - the tiny filtering units within the kidneys. This results in the leakage of large amounts of protein (primarily albumin) into the urine, a condition known as proteinuria.
The term "nephrosis" was often used interchangeably with "minimal change nephropathy," which is a specific type of kidney disorder that demonstrates little to no changes in the glomeruli under a microscope, despite significant protein leakage. However, current medical terminology and classifications prefer the use of more precise terms to describe various kidney diseases, such as minimal change disease, focal segmental glomerulosclerosis, or membranous nephropathy, among others.
It is important to consult with a healthcare professional or refer to updated medical resources for accurate and current information regarding kidney diseases and their specific diagnoses.
The Bowman capsule is the initial component of the nephron, which is the functional unit of the kidney. It is a structural and functional part of the renal corpuscle, along with the glomerulus. The Bowman capsule surrounds the glomerulus and serves as a site for filtration, helping to separate small molecules from blood cells and large proteins in the process known as urine formation.
The Bowman capsule is composed of a single layer of epithelial cells called podocytes, which have foot-like processes that interdigitate with each other and form filtration slits. These slits are covered by a thin diaphragm, allowing for the passage of small molecules while retaining larger ones. The space within the Bowman capsule is called the urinary space or Bowman's space, where the filtrate from the blood collects before moving into the tubular system for further processing and eventual excretion as urine.
The Glomerular Basement Membrane (GBM) is a part of the filtration barrier in the nephron of the kidney. It is a thin, porous sheet of extracellular matrix that lies between the glomerular endothelial cells and the visceral epithelial cells (podocytes). The GBM plays a crucial role in the process of ultrafiltration, allowing the passage of water and small molecules while preventing the loss of larger proteins into the urine. It is composed mainly of type IV collagen, laminin, nidogen, and heparan sulfate proteoglycans. Certain kidney diseases, such as Goodpasture's disease and some forms of glomerulonephritis, can involve damage to the GBM.
AIDS-associated nephropathy (AAN) is a kidney disorder that primarily affects individuals with advanced HIV infection. It is characterized by distinctive changes in the structure and function of the glomeruli, which are the tiny filtering units inside the kidneys.
The medical definition of AIDS-associated nephropathy is:
A renal disease associated with advanced HIV infection, characterized by focal segmental glomerulosclerosis (FSGS), collapsing variant or HIV-associated nephropathy (HIVAN) causing proteinuria, azotemia, and progressive decline in kidney function. The condition is more prevalent in certain racial/ethnic groups, such as African Americans, Hispanics, and Native Americans.
AAN is often considered a complication of advanced HIV disease and can lead to end-stage renal failure if not properly managed. Antiretroviral therapy (ART) has been shown to improve outcomes in patients with AAN, although some individuals may still require dialysis or kidney transplantation.
Proteinuria is a medical term that refers to the presence of excess proteins, particularly albumin, in the urine. Under normal circumstances, only small amounts of proteins should be found in the urine because the majority of proteins are too large to pass through the glomeruli, which are the filtering units of the kidneys.
However, when the glomeruli become damaged or diseased, they may allow larger molecules such as proteins to leak into the urine. Persistent proteinuria is often a sign of kidney disease and can indicate damage to the glomeruli. It is usually detected through a routine urinalysis and may be confirmed with further testing.
The severity of proteinuria can vary, and it can be a symptom of various underlying conditions such as diabetes, hypertension, glomerulonephritis, and other kidney diseases. Treatment for proteinuria depends on the underlying cause and may include medications to control blood pressure, manage diabetes, or reduce protein loss in the urine.
The Glomerular Filtration Barrier is a complex structure in the kidney that is responsible for the initial filtration of blood in the nephron. It is made up of three layers: the fenestrated endothelial cells, the glomerular basement membrane (GBM), and the epithelial cells (podocytes) with their interdigitating foot processes. This barrier allows for the filtration of small molecules, such as water and solutes, while preventing the passage of larger molecules, like proteins, into the urinary space. The proper functioning of this barrier is crucial for maintaining normal kidney function and overall health.
Wilms' Tumor 1 (WT1) proteins are a group of transcription factors that play crucial roles in the development of the human body, particularly in the formation of the urinary and reproductive systems. The WT1 gene encodes these proteins, and mutations in this gene have been associated with several diseases, most notably Wilms' tumor, a type of kidney cancer in children.
WT1 proteins contain four domains: an N-terminal transcriptional activation domain, a zinc finger domain that binds to DNA, a nuclear localization signal, and a C-terminal transcriptional repression domain. These proteins regulate the expression of various target genes involved in cell growth, differentiation, and apoptosis (programmed cell death).
Abnormalities in WT1 protein function or expression have been linked to several developmental disorders, including Denys-Drash syndrome, Frasier syndrome, and Wilms' tumor. These conditions are characterized by genitourinary abnormalities, such as kidney dysplasia, ambiguous genitalia, and an increased risk of developing Wilms' tumor.
Nephrotic syndrome is a group of symptoms that indicate kidney damage, specifically damage to the glomeruli—the tiny blood vessel clusters in the kidneys that filter waste and excess fluids from the blood. The main features of nephrotic syndrome are:
1. Proteinuria (excess protein in urine): Large amounts of a protein called albumin leak into the urine due to damaged glomeruli, which can't properly filter proteins. This leads to low levels of albumin in the blood, causing fluid buildup and swelling.
2. Hypoalbuminemia (low blood albumin levels): As albumin leaks into the urine, the concentration of albumin in the blood decreases, leading to hypoalbuminemia. This can cause edema (swelling), particularly in the legs, ankles, and feet.
3. Edema (fluid retention and swelling): With low levels of albumin in the blood, fluids move into the surrounding tissues, causing swelling or puffiness. The swelling is most noticeable around the eyes, face, hands, feet, and abdomen.
4. Hyperlipidemia (high lipid/cholesterol levels): The kidneys play a role in regulating lipid metabolism. Damage to the glomeruli can lead to increased lipid production and high cholesterol levels in the blood.
Nephrotic syndrome can result from various underlying kidney diseases, such as minimal change disease, membranous nephropathy, or focal segmental glomerulosclerosis. Treatment depends on the underlying cause and may include medications to control inflammation, manage high blood pressure, and reduce proteinuria. In some cases, dietary modifications and lifestyle changes are also recommended.
A kidney, in medical terms, is one of two bean-shaped organs located in the lower back region of the body. They are essential for maintaining homeostasis within the body by performing several crucial functions such as:
1. Regulation of water and electrolyte balance: Kidneys help regulate the amount of water and various electrolytes like sodium, potassium, and calcium in the bloodstream to maintain a stable internal environment.
2. Excretion of waste products: They filter waste products from the blood, including urea (a byproduct of protein metabolism), creatinine (a breakdown product of muscle tissue), and other harmful substances that result from normal cellular functions or external sources like medications and toxins.
3. Endocrine function: Kidneys produce several hormones with important roles in the body, such as erythropoietin (stimulates red blood cell production), renin (regulates blood pressure), and calcitriol (activated form of vitamin D that helps regulate calcium homeostasis).
4. pH balance regulation: Kidneys maintain the proper acid-base balance in the body by excreting either hydrogen ions or bicarbonate ions, depending on whether the blood is too acidic or too alkaline.
5. Blood pressure control: The kidneys play a significant role in regulating blood pressure through the renin-angiotensin-aldosterone system (RAAS), which constricts blood vessels and promotes sodium and water retention to increase blood volume and, consequently, blood pressure.
Anatomically, each kidney is approximately 10-12 cm long, 5-7 cm wide, and 3 cm thick, with a weight of about 120-170 grams. They are surrounded by a protective layer of fat and connected to the urinary system through the renal pelvis, ureters, bladder, and urethra.
Membrane proteins are a type of protein that are embedded in the lipid bilayer of biological membranes, such as the plasma membrane of cells or the inner membrane of mitochondria. These proteins play crucial roles in various cellular processes, including:
1. Cell-cell recognition and signaling
2. Transport of molecules across the membrane (selective permeability)
3. Enzymatic reactions at the membrane surface
4. Energy transduction and conversion
5. Mechanosensation and signal transduction
Membrane proteins can be classified into two main categories: integral membrane proteins, which are permanently associated with the lipid bilayer, and peripheral membrane proteins, which are temporarily or loosely attached to the membrane surface. Integral membrane proteins can further be divided into three subcategories based on their topology:
1. Transmembrane proteins, which span the entire width of the lipid bilayer with one or more alpha-helices or beta-barrels.
2. Lipid-anchored proteins, which are covalently attached to lipids in the membrane via a glycosylphosphatidylinositol (GPI) anchor or other lipid modifications.
3. Monotopic proteins, which are partially embedded in the membrane and have one or more domains exposed to either side of the bilayer.
Membrane proteins are essential for maintaining cellular homeostasis and are targets for various therapeutic interventions, including drug development and gene therapy. However, their structural complexity and hydrophobicity make them challenging to study using traditional biochemical methods, requiring specialized techniques such as X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and single-particle cryo-electron microscopy (cryo-EM).
Diabetic nephropathy is a kidney disease that occurs as a complication of diabetes. It is also known as diabetic kidney disease (DKD). This condition affects the ability of the kidneys to filter waste and excess fluids from the blood, leading to their accumulation in the body.
Diabetic nephropathy is caused by damage to the small blood vessels in the kidneys, which can occur over time due to high levels of glucose in the blood. This damage can lead to scarring and thickening of the kidney's filtering membranes, reducing their ability to function properly.
Symptoms of diabetic nephropathy may include proteinuria (the presence of protein in the urine), edema (swelling in the legs, ankles, or feet due to fluid retention), and hypertension (high blood pressure). Over time, if left untreated, diabetic nephropathy can progress to end-stage kidney disease, which requires dialysis or a kidney transplant.
Preventing or delaying the onset of diabetic nephropathy involves maintaining good control of blood sugar levels, keeping blood pressure under control, and making lifestyle changes such as quitting smoking, eating a healthy diet, and getting regular exercise. Regular monitoring of kidney function through urine tests and blood tests is also important for early detection and treatment of this condition.
Glomerulonephritis is a medical condition that involves inflammation of the glomeruli, which are the tiny blood vessel clusters in the kidneys that filter waste and excess fluids from the blood. This inflammation can impair the kidney's ability to filter blood properly, leading to symptoms such as proteinuria (protein in the urine), hematuria (blood in the urine), edema (swelling), hypertension (high blood pressure), and eventually kidney failure.
Glomerulonephritis can be acute or chronic, and it may occur as a primary kidney disease or secondary to other medical conditions such as infections, autoimmune disorders, or vasculitis. The diagnosis of glomerulonephritis typically involves a combination of medical history, physical examination, urinalysis, blood tests, and imaging studies, with confirmation often requiring a kidney biopsy. Treatment depends on the underlying cause and severity of the disease but may include medications to suppress inflammation, control blood pressure, and manage symptoms.
I'm sorry for any confusion, but a specific medical definition for 'Cyclin I' could not be found. Cyclins are a family of proteins that regulate the cell cycle in cells. They are so named because their levels fluctuate or cycle during different phases of the cell cycle. However, there is no specific cyclin referred to as "Cyclin I" in current medical and scientific literature.
There is a protein called "cyclin I" found in some organisms like Drosophila melanogaster (fruit flies), but it doesn't have a well-established role or equivalent in human cell cycle regulation. Therefore, it may not be relevant to provide a medical definition for a protein that is not directly involved in human physiology or pathophysiology.
Membranous glomerulonephritis (MGN) is a kidney disorder that leads to the inflammation and damage of the glomeruli, which are the tiny blood vessels in the kidneys responsible for filtering waste and excess fluids from the blood. In MGN, the membrane that surrounds the glomerular capillaries becomes thickened and damaged due to the deposit of immune complexes, primarily composed of antibodies and antigens.
The onset of membranous glomerulonephritis can be either primary (idiopathic) or secondary to various underlying conditions such as autoimmune diseases (like systemic lupus erythematosus), infections (hepatitis B or C, syphilis, endocarditis), medications, or malignancies.
The symptoms of membranous glomerulonephritis may include:
1. Proteinuria - the presence of excess protein, specifically albumin, in the urine. This can lead to nephrotic syndrome, characterized by heavy protein loss in urine, edema (swelling), hypoalbuminemia (low blood albumin levels), and hyperlipidemia (high blood lipid levels).
2. Hematuria - the presence of red blood cells in the urine, which can be visible or microscopic.
3. Hypertension - high blood pressure.
4. Edema - swelling in various body parts due to fluid retention.
5. Nephrotic range proteinuria (protein loss greater than 3.5 grams per day) and/or nephritic syndrome (a combination of hematuria, proteinuria, hypertension, and kidney dysfunction) can be observed in some cases.
The diagnosis of membranous glomerulonephritis typically involves a thorough medical history, physical examination, urinalysis, blood tests, and imaging studies. A definitive diagnosis often requires a kidney biopsy to assess the glomerular structure and the nature of the immune complex deposits. Treatment depends on the underlying cause and severity of the disease and may include corticosteroids, immunosuppressants, blood pressure management, and supportive care for symptoms like edema and proteinuria.
"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.
Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.
It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.
Lipoid nephrosis is a historical term for a kidney disorder now more commonly referred to as minimal change disease (MCD). It is a type of glomerulonephritis which is characterized by the loss of proteins in the urine (proteinuria) due to damage to the glomeruli, the tiny filtering units within the kidneys.
The term "lipoid" refers to the presence of lipids or fats in the glomeruli, which can be observed under a microscope. However, it's worth noting that not all cases of MCD involve lipid accumulation in the glomeruli.
MCD is typically idiopathic, meaning its cause is unknown, but it can also occur as a secondary condition related to other medical disorders such as allergies, infections, or medications. It primarily affects children, but can also occur in adults. Treatment usually involves corticosteroids and other immunosuppressive therapies to control proteinuria and prevent kidney damage.
Denys-Drash Syndrome is a rare genetic disorder that affects the kidneys and genitalia. It is characterized by the development of Wilms' tumor, a type of kidney cancer, and abnormal genital development in males. The syndrome is caused by mutations in the WT1 gene, which plays a crucial role in the development of the kidneys and genitalia.
Individuals with Denys-Drash Syndrome typically have underdeveloped or absent male genitalia, and some may be born with ambiguous genitalia. They are also at an increased risk of developing Wilms' tumor, often during the first two years of life. In addition, many individuals with the syndrome develop kidney disease, which can progress to end-stage renal failure.
The management of Denys-Drash Syndrome typically involves close monitoring for the development of Wilms' tumor and kidney disease, as well as treatment with chemotherapy or radiation therapy if necessary. Kidney transplantation may also be required in cases of end-stage renal failure.
Sialglycoproteins are a type of glycoprotein that have sialic acid as the terminal sugar in their oligosaccharide chains. These complex molecules are abundant on the surface of many cell types and play important roles in various biological processes, including cell recognition, cell-cell interactions, and protection against proteolytic degradation.
The presence of sialic acid on the outermost part of these glycoproteins makes them negatively charged, which can affect their interaction with other molecules such as lectins, antibodies, and enzymes. Sialglycoproteins are also involved in the regulation of various physiological functions, including blood coagulation, inflammation, and immune response.
Abnormalities in sialglycoprotein expression or structure have been implicated in several diseases, such as cancer, autoimmune disorders, and neurodegenerative conditions. Therefore, understanding the biology of sialoglycoproteins is important for developing new diagnostic and therapeutic strategies for these diseases.
Albuminuria is a medical condition that refers to the presence of albumin in the urine. Albumin is a type of protein normally found in the blood, but not in the urine. When the kidneys are functioning properly, they prevent large proteins like albumin from passing through into the urine. However, when the kidneys are damaged or not working correctly, such as in nephrotic syndrome or other kidney diseases, small amounts of albumin can leak into the urine.
The amount of albumin in the urine is often measured in milligrams per liter (mg/L) or in a spot urine sample, as the albumin-to-creatinine ratio (ACR). A small amount of albumin in the urine is called microalbuminuria, while a larger amount is called macroalbuminuria or proteinuria. The presence of albuminuria can indicate kidney damage and may be a sign of underlying medical conditions such as diabetes or high blood pressure. It is important to monitor and manage albuminuria to prevent further kidney damage and potential complications.
Mesangial cells are specialized cells that are found in the mesangium, which is the middle layer of the glomerulus in the kidney. The glomerulus is a network of capillaries where blood filtration occurs. Mesangial cells play an important role in maintaining the structure and function of the glomerulus. They help regulate the size of the filtration slits between the capillary endothelial cells and the podocytes (specialized epithelial cells) by contracting and relaxing, similar to smooth muscle cells. Additionally, mesangial cells can phagocytize immune complexes and other debris in the glomerulus, contributing to the body's immune response. They also produce extracellular matrix components that provide structural support for the glomerulus. Mesangial cell dysfunction or injury can contribute to kidney diseases such as glomerulonephritis and diabetic nephropathy.
Kidney disease, also known as nephropathy or renal disease, refers to any functional or structural damage to the kidneys that impairs their ability to filter blood, regulate electrolytes, produce hormones, and maintain fluid balance. This damage can result from a wide range of causes, including diabetes, hypertension, glomerulonephritis, polycystic kidney disease, lupus, infections, drugs, toxins, and congenital or inherited disorders.
Depending on the severity and progression of the kidney damage, kidney diseases can be classified into two main categories: acute kidney injury (AKI) and chronic kidney disease (CKD). AKI is a sudden and often reversible loss of kidney function that occurs over hours to days, while CKD is a progressive and irreversible decline in kidney function that develops over months or years.
Symptoms of kidney diseases may include edema, proteinuria, hematuria, hypertension, electrolyte imbalances, metabolic acidosis, anemia, and decreased urine output. Treatment options depend on the underlying cause and severity of the disease and may include medications, dietary modifications, dialysis, or kidney transplantation.
Transgenic mice are genetically modified rodents that have incorporated foreign DNA (exogenous DNA) into their own genome. This is typically done through the use of recombinant DNA technology, where a specific gene or genetic sequence of interest is isolated and then introduced into the mouse embryo. The resulting transgenic mice can then express the protein encoded by the foreign gene, allowing researchers to study its function in a living organism.
The process of creating transgenic mice usually involves microinjecting the exogenous DNA into the pronucleus of a fertilized egg, which is then implanted into a surrogate mother. The offspring that result from this procedure are screened for the presence of the foreign DNA, and those that carry the desired genetic modification are used to establish a transgenic mouse line.
Transgenic mice have been widely used in biomedical research to model human diseases, study gene function, and test new therapies. They provide a valuable tool for understanding complex biological processes and developing new treatments for a variety of medical conditions.
A "cell line, transformed" is a type of cell culture that has undergone a stable genetic alteration, which confers the ability to grow indefinitely in vitro, outside of the organism from which it was derived. These cells have typically been immortalized through exposure to chemical or viral carcinogens, or by introducing specific oncogenes that disrupt normal cell growth regulation pathways.
Transformed cell lines are widely used in scientific research because they offer a consistent and renewable source of biological material for experimentation. They can be used to study various aspects of cell biology, including signal transduction, gene expression, drug discovery, and toxicity testing. However, it is important to note that transformed cells may not always behave identically to their normal counterparts, and results obtained using these cells should be validated in more physiologically relevant systems when possible.
The glomerular mesangium is a part of the nephron in the kidney. It is the region located in the middle of the glomerular tuft, where the capillary loops of the glomerulus are surrounded by a network of extracellular matrix and mesangial cells. These cells and matrix play an important role in maintaining the structure and function of the filtration barrier in the glomerulus, which helps to filter waste products from the blood.
The mesangial cells have contractile properties and can regulate the flow of blood through the capillaries by constricting or dilating the diameter of the glomerular capillary loops. They also play a role in immune responses, as they can phagocytize immune complexes and release cytokines and growth factors that modulate inflammation and tissue repair.
Abnormalities in the mesangium can lead to various kidney diseases, such as glomerulonephritis, mesangial proliferative glomerulonephritis, and diabetic nephropathy.
Microfilament proteins are a type of structural protein that form part of the cytoskeleton in eukaryotic cells. They are made up of actin monomers, which polymerize to form long, thin filaments. These filaments are involved in various cellular processes such as muscle contraction, cell division, and cell motility. Microfilament proteins also interact with other cytoskeletal components like intermediate filaments and microtubules to maintain the overall shape and integrity of the cell. Additionally, they play a crucial role in the formation of cell-cell junctions and cell-matrix adhesions, which are essential for tissue structure and function.
Zonula Occludens-1 (ZO-1) protein is a tight junction (TJ) protein, which belongs to the membrane-associated guanylate kinase (MAGUK) family. It plays a crucial role in the formation and maintenance of tight junctions, which are complex structures that form a barrier between neighboring cells in epithelial and endothelial tissues.
Tight junctions are composed of several proteins, including transmembrane proteins and cytoplasmic plaque proteins. ZO-1 is one of the major cytoplasmic plaque proteins that interact with both transmembrane proteins (such as occludin and claudins) and other cytoskeletal proteins to form a network of protein interactions that maintain the integrity of tight junctions.
ZO-1 has multiple domains, including PDZ domains, SH3 domains, and a guanylate kinase-like domain, which allow it to interact with various binding partners. It is involved in regulating paracellular permeability, cell polarity, and signal transduction pathways that control cell proliferation, differentiation, and survival.
Mutations or dysfunction of ZO-1 protein have been implicated in several human diseases, including inflammatory bowel disease, cancer, and neurological disorders.
Actinin is a protein that belongs to the family of actin-binding proteins. It plays an important role in the organization and stability of the cytoskeleton, which is the structural framework of a cell. Specifically, actinin crosslinks actin filaments into bundles or networks, providing strength and rigidity to the cell structure. There are several isoforms of actinin, with alpha-actinin and gamma-actinin being widely studied. Alpha-actinin is found in the Z-discs of sarcomeres in muscle cells, where it helps anchor actin filaments and maintains the structural integrity of the muscle. Gamma-actinin is primarily located at cell-cell junctions and participates in cell adhesion and signaling processes.
Immunoelectron microscopy (IEM) is a specialized type of electron microscopy that combines the principles of immunochemistry and electron microscopy to detect and localize specific antigens within cells or tissues at the ultrastructural level. This technique allows for the visualization and identification of specific proteins, viruses, or other antigenic structures with a high degree of resolution and specificity.
In IEM, samples are first fixed, embedded, and sectioned to prepare them for electron microscopy. The sections are then treated with specific antibodies that have been labeled with electron-dense markers, such as gold particles or ferritin. These labeled antibodies bind to the target antigens in the sample, allowing for their visualization under an electron microscope.
There are several different methods of IEM, including pre-embedding and post-embedding techniques. Pre-embedding involves labeling the antigens before embedding the sample in resin, while post-embedding involves labeling the antigens after embedding. Post-embedding techniques are generally more commonly used because they allow for better preservation of ultrastructure and higher resolution.
IEM is a valuable tool in many areas of research, including virology, bacteriology, immunology, and cell biology. It can be used to study the structure and function of viruses, bacteria, and other microorganisms, as well as the distribution and localization of specific proteins and antigens within cells and tissues.
Actin is a type of protein that forms part of the contractile apparatus in muscle cells, and is also found in various other cell types. It is a globular protein that polymerizes to form long filaments, which are important for many cellular processes such as cell division, cell motility, and the maintenance of cell shape. In muscle cells, actin filaments interact with another type of protein called myosin to enable muscle contraction. Actins can be further divided into different subtypes, including alpha-actin, beta-actin, and gamma-actin, which have distinct functions and expression patterns in the body.
Transient Receptor Potential Canonical (TRPC) cation channels are a subfamily of the TRP superfamily of non-selective cation channels. They are widely expressed in various tissues and play crucial roles in many cellular processes, including sensory perception, cell proliferation, and migration. TRPC channels are permeable to both monovalent (sodium and potassium) and divalent (calcium and magnesium) cations, and their activation can lead to a rise in intracellular calcium concentration, which in turn regulates various downstream signaling pathways. TRPC channels can be activated by a variety of stimuli, including G protein-coupled receptors, receptor tyrosine kinases, and mechanical stress. Mutations in TRPC genes have been associated with several human diseases, including hereditary hearing loss, cardiovascular disorders, and neurological conditions.
Epithelial cells are types of cells that cover the outer surfaces of the body, line the inner surfaces of organs and glands, and form the lining of blood vessels and body cavities. They provide a protective barrier against the external environment, regulate the movement of materials between the internal and external environments, and are involved in the sense of touch, temperature, and pain. Epithelial cells can be squamous (flat and thin), cuboidal (square-shaped and of equal height), or columnar (tall and narrow) in shape and are classified based on their location and function.
Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.
IGA glomerulonephritis (also known as Berger's disease) is a type of glomerulonephritis, which is a condition characterized by inflammation of the glomeruli, the tiny filtering units in the kidneys. In IgA glomerulonephritis, the immune system produces an abnormal amount of IgA antibodies, which deposit in the glomeruli and cause inflammation. This can lead to symptoms such as blood in the urine, protein in the urine, and swelling in the legs and feet. In some cases, it can also lead to kidney failure. The exact cause of IgA glomerulonephritis is not known, but it is often associated with other conditions such as infections, autoimmune diseases, and certain medications.