Stroke is one of the leading causes of mortality worldwide. Studies aiming to find new therapeutic methods improving patients outcome afterwards are conducted in the field of stem cell research. Adipose stem cells (ASC) may possess neuroprotective ability and they have shown a potential for helping neuronal cells suffered from ischemic injury to regenerate. The aim of the present research is to develop an in vitro ischemia model for studying ASC possible paracrine effect on damaged neuronal cells. Neuronal cells used in this study were differentiated from human neuroblastoma cell line, SH-SY5Y cells. In vitro ischemia was caused by oxygen-glucose deprivation (OGD) treatment ...
α-smooth muscle actin (α-SMA)-positive cardiac myofibroblasts (CMF) release paracrine mediators that affect cardiomyocyte (CM) structure and function. However, studies have used cardiac fibroblasts (CF) isolated from healthy hearts and activated to CMFs by culture. Whether freshly isolated SMA-negative CFs from healthy hearts affect CM structure and function and whether these effects are altered in CFs after pathological stimulation is unknown. We studied rat LV CFs freshly isolated from normal hearts (sham operated - S CF) and from hearts undergoing thoracic aortic constriction for 10 weeks (T CF). Within 24 hours of isolation CFs were cultured on Transwells above isolated adult rat LV myocytes to allow only paracrine communication (S CF+CM or T CF+CM). CMs co-cultured with other CMs were used as control (CM+CM). After 20 hours we measured adult CM size, contractility and Ca2+ handling. CM volume, assessed by Di-8-ANEPPS staining, was increased in S CF+CM and T CF+CM vs. CM+CM (µm3: CM+CM ...
We have previously demonstrated that mesenchymal stem cells (MSC), when injected into rodent hearts following myocardial infarction (MI), enhance myocardial rep...
Despite recent advances, many cancers remain refractory to available immunotherapeutic strategies. Emerging evidence indicates that the tolerization of local dendritic cells (DCs) within the tumor microenvironment promotes immune evasion. Here, we have described a mechanism by which melanomas establish a site of immune privilege via a paracrine Wnt5a-β-catenin-peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway that drives fatty acid oxidation (FAO) in DCs by upregulating the expression of the carnitine palmitoyltransferase-1A (CPT1A) fatty acid transporter. This FAO shift increased the protoporphyrin IX prosthetic group of indoleamine 2,3-dioxgenase-1 (IDO) while suppressing interleukin(IL)-6 and IL-12 cytokine expression, culminating in enhanced IDO activity and the generation of regulatory T cells. We demonstrated that blockade of this pathway augmented anti-melanoma immunity, enhanced the activity of anti-PD-1 antibody immunotherapy, and suppressed disease progression ...
Muir C, Chung LW, Carson DD, Farach-Carson MC. Hypoxia increases VEGF-A production by prostate cancer and bone marrow stromal cells and initiates paracrine activation of bone marrow endothelial cells. Clin Exp Metastasis. 2006;23(1):75-86. Abstract ...
The role of the immune response in lung fibrosis and its potential as therapeutic target are not clearly established. Here, we provide evidence for a functional contribution of Fra-2-expressing macrophages to the paracrine activation of fibroblasts and to lung fibrosis (Figure 8F). We identify ColVI as a Fra-2 transcriptional target in macrophages and unravel a profibrogenic role for ColVI in vitro and in vivo. Importantly, inhibiting Fra-2/AP-1 or ColVI is therapeutically relevant in mouse models of lung fibrosis.. The fibrotic phenotype in the Fra-2Tg model of fibrosis is reminiscent of a type 2 cytokine-driven disease with enhanced IL-4 expression, IL-4 pathway signature, eosinophil/neutrophil infiltration, and M(IL-4) macrophage enrichment (25, 28, 46). The contribution of type 2 cytokines, IL-4 and IL-13, to macrophage activation and fibrosis development in different organs is well accepted (4, 47, 48). Lung-specific expression of these cytokines increases after bleomycin treatment, ...
Interleukin 12 (IL-12), a disulfide-linked heterodimeric cytokine produced primarily by macrophages, is composed of light (p35) and heavy (p40) chains. It binds to a receptor on T-cells and natural killer cells, promoting the induction of primarily a TH1 response in vitro and in vivo. To determine whether paracrine IL-12 secretion can alter tumor cell growth or promote antitumor immunity, we have developed a delivery system using genetically engineered fibroblasts in murine tumor models. NIH3T3 cells were stably transfected to express 100-240 units/106 cells/48 h of IL-12 using expression plasmids carrying both the murine p35 and p40 genes of murine IL-12. The effects of paracrine secretion of IL-12 on tumor establishment and vaccination models were examined using the poorly immunogenic murine melanoma cell line (BL-6) in C57BL/6 mice. To determine the effects of IL-12 on tumor formation, nonirradiated BL-6 cells were inoculated s.c. into C57BL/6 mice admixed with NIH3T3 cells transfected with ...
My research program focuses on the regulation of cholangiocyte proliferation/damage during cholangiopathies. My studies have demonstrated the key role of a number of factors such as vascular and nerve factors, melatonin, secretin, biogenic amines and sex hormones (expressed and secreted by cholangiocytes) in the regulation of biliary growth/damage by autocrine/paracrine mechanisms. Proliferating cholangiocytes display a neuroendocrine phenotype and secrete and respond to a number of hormones, neuropeptides and neurotransmitters in autocrine and paracrine signaling mechanisms. My research interests also include determining the interactions that occur between cholangiocytes and other cell types (such as hepatocytes, hepatic stellate cells, and vascular endothelial cells) in the biliary microenvironment during both cholestasis and cholangiocarcinogenesis. My program evaluates the various signaling mechanisms regulating the balance between biliary growth/damage. I have expertise in the areas of ...
Our results demonstrate that platelets release small molecules capable of increasing endothelial cell migration in vitro and provide evidence for the importance of dRP in mediating this response. Thus, the genetic ablation of dRP-generating TP and UP in mouse platelets or the specific inhibition of dRP-generating UP by PTAU in human platelets resulted in significantly reduced ability of protein-free supernatants to induce endothelial transmigration. Similarly, the genetic ablation of dRP-generating TP and UP in mouse platelets reduced the ability of protein-free platelet supernatants to promote endothelial monolayer repair in vitro. Both observations supported the conclusions that dRP at the concentrations released by platelets stimulates endothelial cell migration and that UP is the most important enzyme for platelet generation of this metabolite. In accordance with these conclusions, the addition of exogenous dRP to protein-free platelet supernatants reversed the inhibitory effects that ...
Signals that act locally between cells that are close together are called paracrine signals. Paracrine signals move by diffusion through the extracellular matrix. These types of signals usually elicit quick responses that last only a short amount of time. In order to keep the response localized, paracrine ligand molecules are normally quickly degraded by enzymes or removed by neighboring cells. Removing the signals will reestablish the concentration gradient for the signal, allowing them to quickly diffuse through the intracellular space if released again.. One example of paracrine signaling is the transfer of signals across synapses between nerve cells. A nerve cell consists of a cell body, several short, branched extensions called dendrites that receive stimuli, and a long extension called an axon, which transmits signals to other nerve cells or muscle cells. The junction between nerve cells where signal transmission occurs is called a synapse. A synaptic signal is a chemical signal that ...
978 TGFβ is a proliferation suppressor in untransformed epithelial cells. However, in solid tumors, particularly at later stages of disease, increased TGFβ production by the tumor cells contributes to cancer progression through paracrine stimulation of cells in the tumor micro-environment. We therefore proposed that the blockade of TGFβ1 production by the tumor cells would lead to suppression of tumor growth. In this study we investigated the potential components critical for signaling pathways mediating TGFβ1 production using an siRNA approaches, electrophoretic mobility shift assays (EMSA), EMSA super-shift analysis, and TGFβ1 promoter AP-1 luciferase reporter assays. A TGFβ-sensitive, untransformed rat intestinal epithelial cell line, IEC4-1, and a human colon carcinoma (HCC) cell line, FET, were employed in these studies. FET cells stably transfected with tetracycline-controllable dominant-negative mutants of TGFβ type II receptors (DN RII) were also utilized. Our results indicate ...
Paracrine signaling. A cell acts on nearby target cells by secreting local regulators (e.g., a growth factor), which diffuse to target cells ...
TY - JOUR. T1 - Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases. AU - Webber, Matthew J.. AU - Han, Xiaoqiang. AU - Prasanna Murthy, S. N.. AU - Rajangam, Kanya. AU - Stupp, Samuel I. AU - Lomasney, Jon W.. PY - 2010/12. Y1 - 2010/12. N2 - The mechanism for stem cell-mediated improvement following acute myocardial infarction has been actively debated. We support hypotheses that the stem cell effect is primarily paracrine factor-linked. We used a heparin-presenting injectable nanofibre network to bind and deliver paracrine factors derived from hypoxic conditioned stem cell media to mimic this stem cell paracrine effect. Our self-assembling peptide nanofibres presenting heparin were capable of binding paracrine factors from a medium phase. When these factor-loaded materials were injected into the heart following coronary artery ligation in a mouse ischaemia-reperfusion model of acute myocardial infarction, we found significant ...
Osteen, K.G.; Keller, N.R.; Feltus, F.A.; Melner, M.H., 1999: Paracrine regulation of matrix metalloproteinase expression in the normal human endometrium
Relaxin is a peptide hormone that exerts numerous effects in a variety of tissues across a broad range of species. Although first identified more than 75 years ago interest in relaxin biology has waxed and waned over the years consistent with peaks and troughs of new experimental data on its wide-ranging biological effects and advances in relaxin enabling technologies. Recent insights into species-dependent differences in relaxin biology during pregnancy have once again stimulated a relative surge of interest in the study of relaxins reproductive biology. Identification and pharmacological characterization of orphaned relaxin receptors and exploration of its paracrine effects on pregnancy using genomic and proteomic technologies have succeeded in fueling current interest in relaxin research. Primates and non-primate vertebrates exhibit very disparate profiles of relaxin genomics, proteomics and functional biology. Non-human primates appear to exhibit a very close similarity to humans with respect to
Cancer Stem Cells Regulate Cancer-Associated Fibroblasts via Activation of Hedgehog Signaling in Mammary Gland Tumors Scientists investigated the interactions between cancer stem cells (CSCs) and cancer associated fibroblasts (CAFs) in mammary gland tumors driven by combined activation of Wnt/β-catenin and Hgf/Met signaling in mouse mammary epithelial cells. In this setting, CSCs secreted the hedgehog ligand SHH, which regulated CAFs via paracrine activation of Hedgehog signaling. [Cancer Res] Abstract De-Repression of the RAC Activator ELMO1 in Cancer Stem Cells Drives Progression of TGFβ-Deficient Squamous Cell Carcinoma from Transition Zones Researchers identified a highly tumorigenic cancer stem cell population in a mouse model of transitional epithelial carcinoma and uncovered a mechanism by which loss of TGFβ receptor II mediates invasion and metastasis through de-repression of ELMO1, a RAC-activating guanine exchange factor, specifically in cancer stem cells of transition zone tumors. ...
Introduction: We have previously shown that treatment with epidermacan a novel stem cell derived paracrine factor promoted angiogenesis in vitro accompanied with an increase in angiogenic miRNA expression. Here, we identified novel microRNAs regulated by epidermacan and validated their importance in modulating the epidermacan angiogenic effects in vitro and in vivo.. Methods and Results: Increased levels of pro-angiogenic miRNAs such as miR-10b, miR-21 and miR-424 were discovered in MicroRNA profiling of HUVEC cells treated with epidermacan and then confirmed by qRT-PCR. We also identified miR-874, a relatively unknown miRNA but for its role as a tumor suppressor. Investigation of the downstream microRNA/gene networks revealed that epidermacan regulated known angiogenic genes such as VEGFC, TBX1, HIF-1a and NRP1. Importantly, treatment with epidermacan decreased the levels of HoxD10, a known target of miR-10b in thrombin induced angiogenesis. Inhibition of miR-10b or miR-874 via anti-miR ...
Endocrine System Communication Explain the importance of intercellular communication and describe the mechanism involved. Intercellular communication is important because it assist the nervous system to elongate the long-term process of growth, development, or reproduction. The endocrine system uses chemical messengers to relay information and instructions between cells. One of the mechanisms involved in intercellular communication is know as direct communication this communication is rare but is important when it occurs. This is when two cells of the same type and the cells must be in extensive physical contact. The cells are so close they function as one. The majority of the communication is known as paracrine communication which is where the cell continuously exchanges chemical messages between each other so they are in sink with one another. Compare and contrast the modes of intercellular communication used by the endocrine and nervous systems and discuss the functional significance of the ...
Peteranderl and colleagues define a paracrine communication between macrophages and type II alveolar epithelial cells during influenza infection where IFNα induces macrophage secretion of TRAIL that causes endocytosis of Na,K-ATPase by the alveolar epithelium. This reduction of Na,K-ATPase expression decreases alveolar fluid clearance, which in turn leads to pulmonary edema. Inhibition of the TRAIL signaling pathway has been shown to improve lung injury after influenza infection, and future studies will be needed to determine if blocking this pathway is a viable option in the treatment of ARDS.. ...
For several years there has been considerable interest in stimulating angiogenesis by a variety of growth factors, including the family of fibroblast growth factors (FGF). FGF-5 is a protooncogene known to stimulate cell growth and proliferation in multiple cell types, including cancer.1 The cardiac myocyte can also produce different isoforms of FGFs, eg, it has been shown that the expression of basic FGF increases in hibernating myocardium,2 which was the disease state of interest in the current study published in Circulation Research.3 The most commonly cited effect of FGF-5 in the heart is to promote angiogenesis. Several studies have shown that gene transfer of FGF-5 in the heart increases vessel formation and regional blood flow.4-6 This effect is mediated by a production of FGF-5 by the cardiac myocytes, followed by its release in the extracellular space. In addition, FGF-5 can function as an autocrine/paracrine mechanism of cardiac cell growth and as a cytoprotective mechanism against ...
TY - JOUR. T1 - Endothelial Cell Mediated Promotion of Ciliated Cell Differentiation of Human Airway Basal Cells via Insulin and Insulin-Like Growth Factor 1 Receptor Mediated Signaling. AU - Gomi, Kazunori. AU - Tang, Yongjiang. AU - Arbelaez, Vanessa. AU - Crystal, Ronald. AU - Walters, Matthew S.. PY - 2017/4/1. Y1 - 2017/4/1. N2 - Human airway basal cells (BC) function as stem/progenitor cells of the human airway epithelium, capable of differentiating into ciliated and secretory cells during turnover and repair. The positioning of BC along the basement membrane allows for potential paracrine signaling from non-epithelial cells in the mesenchyme to regulate BC function. Based on the knowledge that interaction between the airway epithelium and mesenchyme is critical for proper maintenance of both tissues, and that endothelial cells (EC) can regulate multiple functions of BC, the present study was designed to help understand the role of BC and EC cross-talk in regulating BC stem/progenitor ...
TY - CONF. T1 - Paracrine effect of membrane vesicles released by mouse mesoangioblast stem cells on non correlated cell types. AU - Geraci, Fabiana. AU - Spinello, Walter. AU - Barreca, Maria Magdalena. AU - Sansiverino, Linda. PY - 2016. Y1 - 2016. N2 - IntroductionMouse mesoangioblasts are vessel-associated multipotent progenitor stem cells, which are able to differentiate into different mesodermal cell types. In our previous paper we have demonstrated that these cells are able to shed in the extracellular environment membrane vesicles (EV), which contain both structural proteins and biological factors such as FGF2 and the two gelatinases MMP2/9. EV represent an important mediator of cell-to-cell communication and are involved in both autocrine and paracrine signalling. Interestingly, there is a bidirectional signalling exchange between stem cell EV and damaged cells. In particular, EV from injured cells can reprogram stem cells to acquire the phenotype of the damaged tissue or conversely EV ...
Diabetes is generally attributed to insulin deficiency, but it has become increasingly evident that glucagon excess accounts for many diabetic manifestations (1). In contrast to the consensus mechanisms by which hyperglycemia initiates insulin secretion, there are fundamentally different ideas regarding how glucagon release is stimulated by hypoglycemia. Current hypotheses fall into three categories. First, it is possible that glucose concentration is measured by extrapancreatic sensors that feed back information to glucagon-releasing α-cells via neurons (2,3). Second, since glucagon release is also regulated independently of neural coupling, glucose sensing may be accomplished within the pancreatic islets by β- and δ-cells that control the α-cells via paracrine release of inhibitory insulin (4), Zn2+ (5), γ-aminobutyric acid (6), or somatostatin (7). Third, there is evidence supporting intrinsic glucose sensing by α-cells. In this category, two hypotheses imply that glucose deficiency ...
NovoPro offers a wide selection of tools for research on cytokines and their receptors. These include high-purity recombinant proteins, high-specific antibodies and ORF cDNA clones.. Cytokines are a large group of proteins, peptides or glycoproteins that are secreted by specific cells of immune system. Cytokines are a category of signaling molecules that mediate and regulate immunity, inflammation and hematopoiesis. Cytokines are produced throughout the body by cells of diverse embryological origin. Cytokine is a general name; other names are defined based on their presumed function, cell of secretion, or target of action. For example, cytokines made by lymphocytes can also be referred to as lymphokines, while interleukins are made by one leukocyte and act on other leukocytes. And chemokines are cytokines with chemotactic activities.. Cytokines may act on the cells that secrete them (autocrine action), on nearby cells (paracrine action), or in some instances on distant cells (endocrine ...
Adenine nucleotides (AdNs) play important roles in immunity and inflammation. Extracellular AdNs, such as adenosine triphosphate (ATP) or nicotinamide adenine dinucleotide (NAD) and their metabolites, act as paracrine messengers by fine-tuning both pro- and anti-inflammatory processes. Moreover, intracellular AdNs derived from ATP or NAD play important roles in many cells of the immune system, including T lymphocytes, macrophages, neutrophils and others. These intracellular AdNs are signaling molecules that transduce incoming signals into meaningful cellular responses, e.g. activation of immune responses against pathogens. ...
β-Catenin phosphorylation plays important roles in modulating its functions, but the effects of different phosphorylated forms of β-catenin in response to heterocellular interaction are unclear. Here we investigated whether distinct modes of phosphorylation on β-catenin could be triggered through heterocellular interactions between endothelial cells (ECs) and smooth muscle cells (SMCs), and the consequent modulation of EC functions. ECs were cocultured with SMCs to initiate direct contact and paracrine interaction. EC-SMC coculture induced EC β-catenin phosphorylations simultaneously at tyrosine 142 (Tyr142) and serine 45/threonine 41 (Ser45/Thr41) at the cytoplasm/nuclei and the membrane, respectively. Treating ECs with SMC-conditional medium induced β-catenin phosphorylation only at Ser45/Thr41. These findings indicate that different phosphorylation effects of EC-SMC coculture were induced through heterocellular direct contact and paracrine effects, respectively. Using specific blocking ...
Because the administration of human CDCs improves cardiac function in a SCID mouse MI model,14 we investigated the release of relevant GFs (VEGF, HGF, and IGF1) by human CSps and CDCs, and the potential contribution of paracrine mechanisms to the beneficial and protective effects of CDC-CM in vitro and of CDC therapy in vivo.. Preliminary screening of human CSp- and CDC-CM revealed that these populations are capable of releasing many different cytokines and growth factors, and provides leading information for future experiments (Figure 2). In the present study, though, we selected VEGF, HGF, and IGF1 as our main candidates for more extensive functional studies.. CSps spontaneously release significant and higher amounts of VEGF, HGF, and IGF1 in vitro than do CDCs, as assessed by ELISA. CDCs secrete only VEGF and HGF, although they maintain the transcription of all their mRNAs (Figure 3). On the other hand, IICSps were able to secrete VEGF at levels comparable to primary CSps, suggesting that at ...
Cancer Associated Fibroblasts (CAFs) are an integral component of the TME, and the majority of breast tumor stroma is comprised of CAFs. Multiple juxtacrine and paracrine interactions occur between cancer cells and CAFs that direct tumor progression. These interactions occur via soluble agents, including cytokines, hormones, growth factors, and secreted microRNAs. Some of these soluble agents induce MAPK activation in tumor cells. Our lab has established that MAPK activation in tumor cells is one of the key mechanisms involved in repression of ER. MAPK activation in tumor cells leads to alteration in miRNA expression. We previously identified a microRNA signature indicative of hyperactive MAPK signaling (hMAPK-miRNA signature) that significantly associated with reduced recurrence-free and overall survival. Here we report that the hMAPK-miRNA signature associates with a high metric of stromal cell infiltrate, and we investigate the role of microRNAs, particularly hMAPK-microRNAs, secreted by CAFs on
A hormone (from the Greek participle "ὁρμῶ", "to arouse") is any member of a class of signaling molecules produced by glands in multicellular organisms that are transported by the circulatory system to target distant organs to regulate physiology and behavior. Hormones have diverse chemical structures, mainly of three classes: eicosanoids, steroids, and amino acid/protein derivatives (amines, peptides, and proteins). The glands that secrete hormones comprise the endocrine signaling system. The term hormone is sometimes extended to include chemicals produced by cells that affect the same cell (autocrine or intracrine signalling) or nearby cells (paracrine signalling). Hormones are used to communicate between organs and tissues for physiological regulation and behavioral activities, such as digestion, metabolism, respiration, tissue function, sensory perception, sleep, excretion, lactation, stress, growth and development, movement, reproduction, and mood.[1][2] Hormones affect distant cells ...
Research: hormone/paracrine/autocrine regulation of the renal microcirculation, calcium signaling in vascular smooth muscle cells, pathophysiology of hypertension ...
TY - JOUR. T1 - Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects. AU - Yoshida, Tadashi. AU - Hata, Ryuji. AU - Hakuba, Nobuhiro. AU - Cao, Fang. AU - Zhu, Pengxiang. AU - Sakanaka, Masahiro. AU - Gyo, Kiyofumi. PY - 2007/11/13. Y1 - 2007/11/13. N2 - Background and aims: Idiopathic sudden hearing loss (ISHL) is usually unilateral and can be anything within a range of a slight impairment of hearing to virtual deafness. One of the most common etiologies for ISHL is circulatory disturbance (most often vertebrobasilar ischemia). Vertebrobasilar ischemia (VBI) causes deafness because most of the auditory system including the inner ears is supplied from the vertebrobasilar system. ISHL of vascular cause is important for neurologists to recognize, because it sometimes appears as a warning sign of impending vertebrobasilar ischemic stroke. Previously, we produced cochlear ischemia by occluding both vertebral arteries in gerbils and established ...
TY - JOUR. T1 - DLC1 negatively regulates angiogenesis in a paracrine fashion. AU - Shih, Yi Ping. AU - Liao, Yi Chun. AU - Lin, Yuan. AU - Lo, Su Hao. PY - 2010/11/1. Y1 - 2010/11/1. N2 - The Rho GTPase-activating protein DLC1 is a tumor suppressor that is often deleted in liver cancer and downregulated in other cancers. DLC1 regulates the actin cytoskeleton, cell shape, adhesion, migration, and proliferation through its Rho GTPase-activating protein activity and focal adhesion localization. In this study, we silenced DLC1 in nonmalignant prostate epithelial cells to explore its tumor suppression functions. Small hairpin RNA-mediated silencing of DLC1 was insufficient to promote more aggressive phenotypes associated with tumor cell growth. In contrast, DLC1 silencing promoted pro-angiogenic responses through vascular endothelial growth factor (VEGF) upregulation, accompanied by the accumulation of hypoxia-inducible factor 1α and its nuclear localization. Notably, modulation of VEGF expression ...
Introduction: Macrophages comprise an essential component of the mammary microenvironment necessary for normal gland development. However, there is no viable in vivo model to study their role in normal human breast function. We hypothesized that adding primary human macrophages to the murine mammary gland would enhance and provide a novel approach to examine immune-stromal cell interactions during the humanization process. Methods: Primary human macrophages, in the presence or absence of ectopic estrogen stimulation, were used to humanize mouse mammary glands.
Because of a huge amount of Zn2+ in secretory granules of pancreatic islet beta-cells, Zn2+ released in certain conditions might affect the function or survival of islet cells. We studied potential paracrine effects of endogenous Zn2+ on beta-cell death. Zn2+ induced insulinoma/islet cell death in a dose-dependent manner. Chelation of released endogenous Zn2+ by CaEDTA significantly decreased streptozotocin (STZ)-induced islet cell death in an in vitro culture system simulating in vivo circumstances but not in the conventional culture system. Zn2+ chelation in vivo by continuous CaEDTA infusion significantly decreased the incidence of diabetes after STZ administration. N-(6-methoxy-quinolyl)-para-toluene-sulfonamide staining revealed that Zn2+ was densely deposited in degenerating islet cells 24 h after STZ treatment, which was decreased by CaEDTA infusion. We show here that Zn2+ is not a passive element for insulin storage but an active participant in islet cell death in certain conditions, ...
After completing his clinical training in Cardiology, Prof. Massimiliano Gnecchi moved to the USA to work as a postdoctoral research fellow and research associate at Harvard and Duke University. During that time, he studied the mechanisms of action through which adult stem cells heal infarcted hearts. After winning a prestigious National Research Award, Prof. Gnecchi relocated to Italy and became an independent investigator. He is currently Associate Professor of Cardiology at Pavia University and Cardiologist at the Fondazione IRCCS San Matteo Pavia. He is the Director of the Research and Clinical Laboratories of the Department of Cardiology in Pavia. His current research interests are stem cell paracrine mechanisms, and use of iPSC for disease modelling and drug testing.. ...
NSL3 could also have important endocrine or paracrine roles in other tissues. Although defective spermatogenesis found in INSL3 or LGR8 null mice could be the secondary effects of cryptorchidism, Leydig cell-derived INSL3 could play a paracrine role in the testis because LGR8 is also expressed in the testis. In females, INSL3 is expressed in the luteal cells of the ovary through the estrous cycle and during pregnancy [1] ...
Whereas it is clear that Parv+ inhibitory synapses are essential for controlling the flow of neuronal activity, the mechanisms underlying the formation of these synapses are not well understood. Here we discovered that a neuronally expressed collagen contributes to the development of these synapses. Deletion of this collagen results in reduced numbers of inhibitory synapses, and specifically axosomatic inhibitory synapses, so it is not surprising that col19a1−/− mutant mice display a range a behavioral phenotypes, including neglect, impairment in sensorimotor gating, and seizures. It is surprising, however, that the majority of cells generating collagen XIX are not presynaptic Parv+ interneurons or their postsynaptic targets (Fig. S5 D). This suggests a novel paracrine mechanism that contributes to Parv+ inhibitory synapse formation and sheds new light on why patients with microdeletions in the genomic region encoding collagen XIX may suffer from schizophrenia (Liao et al., 2012).. As with ...
This gene encodes a secreted, homodimeric glycoprotein that is expressed in a wide variety of tissues and may have autocrine or paracrine functions. The gene contains a 5 UTR rich in CAG trinucleotide repeats. The encoded protein contains 11 conserved cysteine residues and is phosphorylated by protein kinase C exclusively on its serine residues. The protein may play a role in the regulation of renal and intestinal calcium and phosphate transport, cell metabolism, or cellular calcium/phosphate homeostasis. Overexpression of human stanniocalcin 1 in mice produces high serum phosphate levels, dwarfism, and increased metabolic rate. This gene has altered expression in hepatocellular, ovarian, and breast cancers ...
read more] This gene encodes a secreted, homodimeric glycoprotein that is expressed in a wide variety of tissues and may have autocrine or paracrine functions. The encoded protein has 10 of its 15 cysteine residues conserved among stanniocalcin family members and is ...
tokine and gene-transfer therapeutic approaches. Therefore, we undertook a study to assess the antitumor effects induced by the local production of IL-12 within MM tumors by transfecting a murine MM line with the genes for IL-12. The IL-12 transfectant (AB1-IL-12) did not produce tumors in normal mice, but did so in athymic nude mice, implicating T cells in the prevention of MM tumor growth. In mixing experi- ments, paracrine IL-12 production inhibited growth of untransfected MM cells provided that cells produc- ing IL-12 represented more than 50-80% of the inoculum. Furthermore, BALB/c mice previously chal- lenged with AB1-IL-12 were protected against rechallenge with parental AB1 tumor, indicating that ...
John Condeelis is The Judith and Burton P. Resnick Chair in Translational Research, Professor and Co-Chairman of the Department of Anatomy and Structural Biology at the Albert Einstein College of Medicine (AECOM). He is the director of the Cancer Center program "Tumor microenvironment and Metastasis" and co-Director of the Gruss Lipper Biophotonics Center of AECOM, a center dedicated to the development and application of optical imaging technologies. He is co-Director of the Integrated Imaging Program which is dedicated to the translation of methods using combined imaging modalities into clinically useful prognostics and treatment endpoints.. His research interests are in optical physics, cell biology and biophysics, cancer biology and mouse models of cancer. He and his collaborators developed the multiphoton imaging technology and animal models used to identify invasion and intravasation microenvironments in mammary tumors. This led to the discovery of the paracrine interaction between tumor ...
Genetic alterations in tumor cells often lead to the emergence of growth-stimulatory autocrine and paracrine signals, involving overexpression of secreted peptide growth factors, cytokines, and hormones. Increased levels of these soluble proteins may be exploited for cancer diagnosis and management or as points of therapeutic intervention. Here, we combined the use of controlled vocabulary terms and sequence-based algorithms to predict genes encoding secreted proteins from among approximately 12,500 sequences represented on oligonucleotide microarrays. Expression of these genes was queried in 150 carcinomas from 10 anatomic sites of origin and compared with 46 normal tissues derived from the corresponding sites of tumor origin and other body tissues and organs. Of 74 different genes identified as overexpressed in cancer tissues, several encode proteins with demonstrated clinical diagnostic application, such as alpha-fetoprotein in liver carcinoma, and kallikreins 6 and 10 in ovarian cancer, or
Astrocytes are secretory cells highly, participating in quick brain communication by releasing glutamate. of such component is sustained by autocrine/paracrine action of PGE2. 1. Intro The morphology and the location of astrocytes place them in a unique position to be able to listen and respond to neuronal activity [1C5]. Astrocytes communicate a wide variety of practical neurotransmitter receptors essential for sensing neuronal activity [6]. Many of these receptors are G-protein-coupled receptors (GPCRs) that, upon activation, stimulate phospholipase C and form inositol (1,4,5)-triphosphate (IP3) which increases the intracellular calcium (Ca2+) concentration through the release of Ca2+ from intracellular stores [6]. The intracellular cascade resulting in Ca2+ rise in astrocytes is the main mechanism these cells use to transduce synaptic activity. It is well established the GPCR- mediated Ca2+ variations in astrocytes can result in launch of chemical substances [7, 8] such as excitatory amino ...
Poor clinical outcomes of tendon repair, together with limited regenerative capacity of the tissue, have triggered the search for alternative regenerative medicine strategies. Human adipose-derived stem cells (hASCs) are being investigated as a promising cell source in contributing for tendon repopulation and reconstruction. However, the mechanisms involved in a potential beneficial effect in tendon regeneration are still to be uncovered. To gain further insights on the bi-directional crosstalk occurring between stem cells and the native tendon niche, it was used an indirect (trans-well) system for co-culturing human tendon explants and hASCs. The maintenance of tissue architecture was studied up to 14 days by histological techniques. The secretion of MMPs was evaluated at day 3. The behavior of hASCs was assessed regarding cell elongation and extracellular matrix (ECM) production. The paracrine communication enhanced collagenolytic activity of MMPs in co-cultures at day 3, in comparison to ...
Silencing prolyl hydroxylase domain protein 2 (PHD2) promotes the survival of transplanted adipose-derived stem cells (ADSCs) in infarcted hearts and enhances their paracrine function. The promoted survival was HIF-1alpha dependent, while the enhanced paracrine function was associated with NF-kB signaling. ...
Although advanced esophageal squamous-cell carcinoma (ESCC) is treated using a multidisciplinary approach, outcomes remain unsatisfactory. The microenvironment of cancer cells has recently been shown to strongly influence the biologic properties of malignancies. We explored the effect of supernatant from esophageal fibroblasts on the cell growth and chemo-resistance of ESCC cell lines. We used 22 ESCC cell lines, isolated primary human esophageal fibroblasts and immortalized fibroblasts. We first examined cell proliferation induced by fibroblast supernatant. The effect of supernatant was evaluated to determine whether paracrine signaling induced by fibroblasts can influence the proliferation of cancer cells. Next, we examined the effects of adding growth factors HGF, FGF1, FGF7, and FGF10, to the culture medium of cancer cells. These growth factors are assumed to be present in the culture supernatants of fibroblasts and may exert a paracrine effect on the proliferation of cancer cells. We also examined
Dendritic cells (DCs)3 undergo a composite program in response to microbial components, referred to as maturation. Maturing DCs up-regulate the membrane expression of molecules involved in T cell activation and costimulation, including MHC class I and class II CD40, CD80, and CD86 molecules. This process is necessary for productive activation of naive T cells, which takes place in the lymph nodes (1).. DCs committed to maturation in peripheral tissues reach the lymph nodes through afferent lymphatic vessels: they release inflammatory chemokines, which induce through an autocrine/paracrine loop the down-regulation of the CCR1 and CCR5 chemokine receptors (2). Later on, DCs up-regulate the expression of CCR7 and CXCR4, thus acquiring responsiveness to lymph node chemokines. DCs that do not express CCR7 cannot reach the lymph nodes. Conversely, DC migration abates in mice lacking lymph node chemokines or the γ-isoform of phosphoinositide-3 kinase, which is required for response to chemotactic ...
Colorectal cancer (CRC) is the second leading cause of cancer death in the United States, due to the fact that chemoresistance develops in nearly all patients l...
Keywords: angiogenesis, Compact disc31, engraftment, irritation, myocardial infarction, peripheral vascular disease Cell therapy provides surfaced as a appealing brand-new technique for regenerating broken ischemic tissues. Fresh research and 266359-93-7 IC50 preliminary scientific studies with several bone fragments marrow (BM) cells, BM-mononuclear cells (MNCs), early endothelial progenitor cells (EPCs), or mesenchymal control cells (MSCs) possess proven advantageous results on cardiac fix after myocardial infarction (MI) (1,2). Mechanistically, paracrine activities are today known to end up being the primary system root ischemic tissues fix (3-6). Latest meta-analyses of scientific studies for cardiac cell therapy with BM cells demonstrated that still left ventricular ejection small percentage improved just 4% (7). Remarkably, chosen populations such as Compact disc34+ and Compact disc133+ (also known as prominin 1 [PROM]) cells do not really present 266359-93-7 IC50 significant healing ...
OSM, which is a member of the IL-6 type of cytokines, affects the growth of prostate cells in a paracrine manner (16 , 20) . This is different from IL-6, for which both autocrine and paracrine loops were reported in the prostate (12 , 19) . It is well established that prostate cancer cells PC-3 and DU-145 express IL-6 (20, 21, 22) . Those findings were supported by studies carried out on clinical specimens (12 , 13) . In contrast, OSM was not detected in conditioned media from the cell lines LNCaP ATCC, LNCaP GW that acquires a p53 mutation, PC-3, and DU-145 by ELISA (20 , 21) . On the basis of our results and those of previous reports, we conclude that both IL-6 and OSM activate the AR (6, 7, 8) . However, the unexpected findings of the present study are that hydroxyflutamide acts as an AR agonist in the presence of OSM and that bicalutamide causes inhibition of AR activity only at lower concentrations. In prostate cancer, the switch of nonsteroidal antiandrogens to agonists was reported in ...