Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mechanisms of prepro-ET-1 mRNA expression and mature endothelin-1 (ET-1) peptide secretion in MDCK cells (dog collecting duct origin) were investigated. MDCK cells constitutively expressed prepro-ET-1 mRNA (approximately 2.3 kb). TGF-beta time-dependently increased prepro-ET-1 mRNA levels between 30 min and 6 h. Induction of the mRNA 6 h following TGF-beta addition was dose-dependent with a half-maximal concentration of 10 pM. The half-life of prepro-ET-1 mRNA was 15 min in controls when the cells were treated with 10 micrograms/ml of actinomycin D, whereas it was extended to 30-45 min by TGF-beta treatment. Prepro-ET-1 mRNA was rapidly (15-30 min) induced by 0.5 microM TPA, one of the phorbol esters, but downregulated below baseline after 1 h. Our data show that MDCK cells constitutively secrete ET-1 and increase its production in response to TGF-beta. An axis of TGF-beta-ET-1-collecting duct may play an important role in regulation of electrolyte transport and cell growth of the renal tubules.
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PMID:Mechanisms of endothelin-1 mRNA and peptides induction by TGF-beta and TPA in MDCK cells. 172 39

The renal collecting duct is a major target for the mineralocorticoid hormone aldosterone which acts to enhance electrogenic Na+ absorption. The cortical portion of the collecting duct displays a vigorous response to mineralocorticoids administered in vivo. The terminal, or inner medullary portion, does not usually display such a vigorous response; the reason for this difference is unknown. To explore one possible mechanism for this lack of response, we varied the conditions of culturing these cells and determined that serum inhibited the ability of aldosterone to enhance Na+ transport. By screening 11 peptides, we found that transforming growth factor (TGF)-beta 1 produced a concentration-dependent inhibition of the action of aldosterone. The action of TGF-beta 1 required at least several hours of incubation. Resistance to the action of aldosterone could be produced by preincubating the monolayers with TGF-beta 1 for a few hours; subsequent exposure to aldosterone for up to 48 h failed to stimulate Na+ transport. TGF-beta 1 did not produce a change in cell morphology or the content of DNA, ATP, or ADP; there was a small reduction in protein content. Pretreatment with cycloheximide failed to reproduce the TGF-beta 1 effect. The induction of resistance to mineralocorticoid hormone may play an important role in modulating the effects of aldosterone on Na+ homeostasis.
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PMID:Induction of resistance to mineralocorticoid hormone in cultured inner medullary collecting duct cells by TGF-beta 1. 752 8

Endothelin (ET) is now known to be a family of three distinct peptides. Although many reports have studied the renal action of ET-1, comparatively little is known concerning ET-3. We previously reported that ET-1 mRNA is expressed in glomerulus (Glm) and inner medullary collecting duct (IMCD). In this study, microlocalization of mRNA coding ET-3 was carried out in the rat kidney using a reverse transcription and polymerase chain reaction (RT-PCR) assay of individual microdissected renal tubule segments along the nephron, Glm, vasa recta bundle, and arcuate arteries. Large signals for ET-3 PCR product were detected in proximal convoluted and straight tubules, cortical collecting duct, and outer medullary collecting duct. Glm, IMCD, and vasa recta bundle also expressed relatively large amounts of ET-3 mRNA. Small signals were found in medullary thick ascending limb, inner medullary thin limb, and arcuate artery. We detected ET-3 protein in tubule suspensions from cortex, outer medulla, and inner medulla of rat kidney. Furthermore, incubation with TGF-beta did not change ET-3 PCR signal, whereas ET-1 PCR signal was increased significantly by exposure to TGF-beta in Glm and IMCD. Thus, ET-3 and ET-1 are distributed differently along the nephron and are regulated in different manners. This suggests that ET-3 and ET-1 may affect kidney functions in different ways.
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PMID:Expression of endothelin-3 mRNA along rat nephron segments using polymerase chain reaction. 830 29

Circumstantial evidence from clinical and pathologic correlations in patients with glomerular diseases and proteinuria suggest that glomerular protein ultrafiltration contributes to tubulointerstitial injury. A series of studies was performed to examine the hypothesis that in rats with adriamycin-induced nephropathy or with diabetic nephropathy (but not in normal rats) high molecular wt. growth factors are ultrafiltered into tubular fluid and act on tubular cells through apical membrane receptors. Analysis of proximal tubular fluid that was collected by nephron micropuncture indicates ultrafiltration of IGF-I, TGF-beta and HGF. Respective receptors are also expressed in apical membranes in some parts of the nephron as examined by immunohistochemistry. In vitro cell culture experiments using proximal tubular fluid obtained from rats with experimental glomerular diseases indicate that ultrafiltered IGF-I may contribute to increased distal tubular Na-absorption. Indirect evidence also suggests that this growth factor may increase the secretion of collagen types I and IV in proximal tubular cells. TGF-beta and HGF cause increased expression and basolateral secretion of MCP-1 in proximal tubular and collecting duct cells. There may be other biologic effects on tubules that are caused by apical exposure to ultrafiltered growth factors. These studies suggest that the glomerular ultrafiltration of bioactive proteins causes or contributes to tubulo-interstitial pathology in glomerular proteinuria.
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PMID:Pathophysiologic glomerulotubular growth factor link. 1068 46

The urinary collecting duct system of the permanent kidney develops by growth and branching of an initially unbranched epithelial tubule, the ureteric bud. Formation of the ureteric bud as an outgrowth of the wolffian duct is induced by signalling molecules (such as GDNF) that emanate from the adjacent metanephrogenic mesenchyme. Once it has invaded the mesenchyme, growth and branching of the bud is controlled by a variety of molecules, such as the growth factors GDNF, HGF, TGFbeta, activin, BMP-2, BMP-7, and matrix molecules such as heparan sulphate proteoglycans and laminins. These various influences are integrated by signal transduction systems inside ureteric bud cells, with the MAP kinase, protein kinase A and protein kinase C pathways appearing to play major roles. The mechanisms of morphogenetic change that produce branching remain largely obscure, but matrix metalloproteinases are known to be necessary for the process, and there is preliminary evidence for the involvement of the actin/myosin contractile cytoskeleton in creating branch points.
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PMID:Intracellular and extracellular regulation of ureteric bud morphogenesis. 1132 19

Congenital obstructive nephropathy is a common disease affecting fetuses and young children. The kidney shows profound morphologic and functional changes. The physiologic developmental kidney program is disturbed in the most advanced cases, arguing for altered temporal/spatial expression of genes which control normal nephrogenesis. Major regulators of mesenchymal-epithelial transformation and collecting duct and tubular development such as WT1 and Sall1 are decreased with obstruction. Additional candidate genes include GDNF/cRET, LIM1 and Pax2. Excessive apoptosis is an undisputed mechanism in these processes, mediated by decreased expression of apoptosis inhibiting genes (Bcl-2, HGF, IGF, BMP7), and overexpression of pro-apoptotic genes like Bax and TGF-beta. Renin and AT2R implicated in renal vascular development are decreased. Numerous extracellular matrix genes including Matrilysin are altered. The emerging theories of the biology of congenital obstructive nephropathy suggest new targets for therapeutic interventions with profound implications for these children.
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PMID:Biology of congenital obstructive nephropathy. 1266 Apr 11

Specification of embryonic progenitors to generate the branched collecting duct system and tubular epithelia of the nephron in the metanephros is mediated by families of soluble factors that cooperate to regulate morphogenesis. These include multiple members of the FGF, TGF-beta, and Wnt families; however, the complexity of interactions through cell-cell and extracellular matrix-mediated contacts, the redundancy of factors involved, and multiplicity of cooperative signaling mechanisms limit our understanding of events responsible for this development. With available in vitro and targeted mutagenesis models, we are now beginning to comprehend how the secreted inductive proteins and associated transcription factors direct competent cells to produce a functional filtering tubular epithelium and its tightly integrated vascular network.
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PMID:Renal development: perspectives on a Wnt-dependent process. 1462 18

The TGFbeta superfamily plays diverse and essential roles in kidney development. Gdf11 and Bmp4 are essential for outgrowth and positioning of the ureteric bud, the inducer of metanephric mesenchyme. During nephrogenesis, Bmp7 is required for renewal of the mesenchyme progenitor population. Additionally, in vitro studies demonstrate inhibitory effects of BMPs and TGFbetas on collecting duct branching and growth. Here, we explore the predicted models of TGFbeta superfamily function by cell-specific inactivation of Smad4, a key mediator of TGFbeta signaling. Using a HoxB7cre transgene expressed in ureteric bud and collecting duct, we find that development of the collecting duct is Smad4 independent. By contrast, removal of Smad4 in nephrogenic mesenchyme using the Bmp7(cre/+) allele leads to disorganization of the nephrogenic mesenchyme and impairment of mesenchyme induction. Smad4-deficient metanephric mesenchyme does not display defects in inducibility in LiCl or spinal cord induction assays. However, in situ hybridization and lineage analysis of Smad4 null mesenchyme cells at E11.5 show that the nephrogenic mesenchyme does not aggregate tightly around the ureteric bud tips, but remains loosely associated, embedded within a population of cells expressing markers of both nephrogenic mesenchyme and peripheral stroma. We conclude that the failure of recruitment of nephrogenic mesenchyme leaves a primitive population of mesenchyme at the periphery of the kidney. This population is gradually depleted, and by E16.5 the periphery is composed of cells of stromal phenotype. This study uncovers a novel role for TGFbeta superfamily signaling in the recruitment and/or organization of the nephrogenic mesenchyme at early time-points of kidney development. Additionally, we present conclusive genetic lineage mapping of the collecting duct and nephrogenic mesenchyme.
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PMID:TGFbeta superfamily signals are required for morphogenesis of the kidney mesenchyme progenitor population. 1534 83

The phenomenon of branching morphogenesis is a fundamental process critical for development of several tubular organs including lung, mammary gland, and kidney. In the case of kidney, the ureteric bud (UB) that extends out from a pre-existing epithelial tube, the Wolffian duct, gives rise to the branched collecting duct system while the surrounding metanephric mesenchyme undergoes mesenchymal-epithelial transition to form the proximal parts of the nephron. These events are mediated by several soluble factors that act in a cooperative fashion either as pro or anti tubulogenic factors. Among the growing list of such molecules are the members of the FGF, TGF-beta, and Wnt families as well as GDNF, HGF, and EGF. Cells respond to these soluble factors by initiating signaling pathways that regulate cell proliferation, cell migration and cell morphogenesis. These signaling pathways are also regulated in parallel by cell-cell and cell-matrix interactions, leading to the complex events necessary for tubule formation. Recent in-vitro and in-vivo studies have begun to shed light on the overall regulation of this phenomenon while the specific subcellular mechanisms are only beginning to be understood. This review focuses on our understanding of the morphogenic responses that regulate in-vitro tubulogenesis and how they may help us to ultimately understand this process in vivo in the kidney.
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PMID:Signals which build a tubule. 1573 68

Gain/loss of function studies were utilized to assess the potential role of the endogenous vanilloid receptor TRPV4 as a sensor of flow and osmolality in M-1 collecting duct cells (CCD). TRPV4 mRNA and protein were detectable in M-1 cells and stably transfected HEK-293 cells, where the protein occurred as a glycosylated doublet on Western blots. Immunofluorescence imaging demonstrated expression of TRPV4 at the cell membranes of TRPV4-transfected HEK and M-1 cells and at the luminal membrane of mouse kidney CCD. By using intracellular calcium imaging techniques, calcium influx was monitored in cells grown on coverslips. Application of known activators of TRPV4, including 4alpha-PDD and hypotonic medium, induced strong calcium influx in M-1 cells and TRPV4-transfected HEK-293 cells but not in nontransfected cells. Applying increased flow/shear stress in a parallel plate chamber induced calcium influx in both M-1 and TRPV4-transfected HEK cells but not in nontransfected HEK cells. Furthermore, in loss-of-function studies employing small interference (si)RNA knockdown techniques, transfection of both M-1 and TRPV4-transfected HEK cells with siRNA specific for TRPV4, but not an inappropriate siRNA, led to a time-dependent decrease in TRPV4 expression that was accompanied by a loss of stimuli-induced calcium influx to flow and hypotonicity. It is concluded that TRPV4 displays a mechanosensitive nature with activation properties consistent with a molecular sensor of both fluid flow (or shear stress) and osmolality, or a component of a sensor complex, in flow-sensitive renal CCD.
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PMID:Dual role of the TRPV4 channel as a sensor of flow and osmolality in renal epithelial cells. 1769 50


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