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)

Angiotensin II (Ang II)-mediated hypertension induces vascular smooth muscle cell hypertrophy and hyperplasia in systemic blood vessels, but the effects of Ang II on the intrinsic cell populations within the kidney have been less well characterized. We infused Ang II for 14 days into rats by minipump at doses (200 ng/min) that resulted in moderate hypertension (mean systolic blood pressure 156-172 mm Hg). Small renal arterial vessels of Ang II-infused rats demonstrated focal injury with fibrinoid necrosis and medial hyperplasia, whereas the glomerular capillaries demonstrated only rare segmental hyalinosis. Proliferation of vascular smooth muscle cells was pronounced (fourfold to 20-fold increase in [3H]thymidine incorporation) as opposed to a minimal proliferation of glomerular cells in Ang II-infused rats. In contrast, the principal effect of Ang II in glomeruli was to increase the expression of alpha-smooth muscle actin by mesangial cells and desmin by visceral glomerular epithelial cells. Ang II-infused rats also developed focal tubulointerstitial injury, with tubular atrophy and dilation, cast formation, an interstitial monocytic infiltrate, and mild interstitial fibrosis with increased type IV collagen deposition. The injury was associated with a proliferation of distal tubule, collecting duct, and interstitial cells as determined by immunostaining for proliferating cell nuclear antigen, and was accompanied by an increase in platelet-derived growth factor B-chain messenger RNA in the area of interstitial injury as localized by in situ hybridization. Renal interstitial cells also underwent phenotypic modulation in which they expressed alpha-smooth muscle actin. Vehicle-infused control rats displayed no tubular injury, proliferation, or phenotypic modulation. Thus, Ang II in doses that cause moderate hypertension induces marked vascular, glomerular, and tubulointerstitial injury with cell proliferation, leukocyte recruitment, phenotypic modulation with the upregulation of proteins normally associated with smooth muscle cells, and interstitial fibrosis.
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PMID:Renal injury from angiotensin II-mediated hypertension. 156 65

The roles of growth factors in the pathogenesis of various forms of acute and chronic renal disease are largely putative. Nevertheless, there is a growing body of information that links specific growth factors to particular forms of renal injury. In all instances, it is supposed that such associations are not necessarily unique and that multiple cytokines probably interact to determine the pattern of injury or the regenerative response to such injury. Regeneration of tubular epithelium after acute tubular necrosis involves upregulation of the epidermal growth factor (EGF) receptor. Early studies of exogenously administered EGF indicate that the severity and duration of renal failure may be attenuated by this growth factor. Thus far, the observed responses have been limited and the role of EGF as a therapeutic agent requires more study. The mechanism of generation of tubulointerstitial injury in most forms of renal disease is difficult to understand. Early in vitro studies of growth factor production by tubular cells (in the absence of any infiltrating cells) indicate that platelet-derived growth factor produced by the medullary collecting duct is mitogenic for renal medullary fibroblasts, suggesting a paracrine growth system in this region of the kidney. Insulin-like growth factor I has also been shown to be produced by collecting duct cells. Its production is increased by EGF, and its association with certain forms of renal hypertrophy, i.e., diabetes and hypersomatotrophic states, implies its participation in the hypertrophic growth response. Platelet-derived growth factor is a potent mitogen for glomerular mesangial cells, and its production is regulated by a variety of cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evolving role of growth factors in the renal response to acute and chronic disease. 159 57

To examine the role of tubulointerstitial cell interaction in the regulation of fibroblast growth, fibroblasts from the rabbit renal cortex (CF) and papilla (PF) were cocultured with epithelial cells from the same tissue location. Inner medullary collecting duct epithelial cells (IMCDE) or IMCDE-conditioned medium stimulated DNA synthesis in PF, whereas proximal tubule epithelium (PTE) had no effect on the proliferation of CF. PF and CF showed a similar mitogenic response to exogenous epidermal growth factor and insulin-like growth factor 1 (IGF-I). Transforming growth factor-beta 1 inhibited growth of both cell types, and basic fibroblast growth factor (bFGF) had no effect on proliferation of either cell type. In contrast, platelet-derived growth factor (PDGF) was a potent mitogen for PF but was only weakly mitogenic for CF. Both CF and PF expressed a similar number of a single-affinity class of PDGF receptors (Kd, 2-4 x 10(-10) M). Assay for growth factor activity in conditioned medium from IMCDE and PTE showed that only IMCDE produced detectable PDGF. IMCDE-stimulated proliferation of PF was partially blocked by an antibody to PDGF, whereas antibodies to IGF-I had no neutralizing effect. The data suggest a role for PDGF in the regulation of interstitial fibroblast proliferation by IMCDE in the renal papilla. This paracrine system may be important in the pathogenesis of some forms of interstitial fibrosis of the kidney.
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PMID:Fibroblasts of rabbit kidney in culture. II. Paracrine stimulation of papillary fibroblasts by PDGF. 165 5

Platelet-derived growth factor-C (PDGF-C) is a new member of the PDGF family. Its expression in normal and diseased kidney is unknown. Rabbit antisera were generated against human full-length, core domain, and mouse PDGF-C, and their specificity was confirmed by Western blot analyses. Renal PDGF-C expression was analyzed by immunohistochemistry in normal rats (n = 8), mesangioproliferative anti-Thy 1.1 nephritis (n = 4 each at days 1, 4, 6, and 85), passive Heymann nephritis (PHN, n = 4), puromycin nephrosis (PAN, n = 2), Milan normotensive rats (MN, n = 2), and obese Zucker rats (n = 3). PDGF-C expression was also studied in anti-Thy 1.1 rats treated with PDGF-B aptamer antagonists (n = 5) or irrelevant control aptamers (n = 5). PDGF-C was constitutively expressed in arterial smooth muscle cells and collecting duct epithelial cells. Mesangial PDGF-C was markedly upregulated in anti-Thy 1.1 nephritis in parallel with the peak mesangial cell proliferation. Furthermore, PDGF-CC acted as a potent growth factor for mesangial cells in vitro. Inhibition of PDGF-B via specific aptamers reduced the injury in anti-Thy 1.1 nephritis but did not affect the glomerular PDGF-C overexpression or the mitogenicity of PDGF-CC in vitro. In PHN, PAN, and obese Zucker rats, glomeruli remained negative for PDGF-C despite severe glomerular injury. PDGF-C localized to podocytes at sites of focal and segmental sclerosis in MN. Interstitial PDGF-C expression was increased at sites of fibrosing injury in obese Zucker rats. The use of the different antisera resulted in virtually identical findings. It is concluded that PDGF-C is a novel mesangial cell mitogen that is constitutively expressed in the kidney and specifically upregulated in mesangial, visceral epithelial, and interstitial cells after predominant injury to these cells. PDGF-C may therefore be involved in the pathogenesis of renal scarring.
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PMID:Expression of a novel PDGF isoform, PDGF-C, in normal and diseased rat kidney. 1191 50

Sodium-hydrogen exchanger regulatory factor-1 and -2 (NHERF-1 and NHERF-2) are adaptor proteins that regulate renal electrolyte transport and interact with the platelet-derived growth factor receptors (PDGFR). The distribution of the NHERF proteins and PDGFR was studied in normal human kidneys and in renal transplant rejection using immunocytochemistry. In normal kidneys, NHERF-1 was detected in proximal tubules. NHERF-2 was detected in glomeruli, peritubular capillaries, and collecting duct principal cells. NHERF-2 was also weakly detected in the proximal tubule. PDGFR-beta was detected in glomeruli but not in tubules while PDGFR-alpha was detected in renal tubules and minimally in glomeruli. Acute and chronic transplant rejection was associated with increased expression of PDGFR-alpha in tubules and expression in the glomeruli. PDGFR-beta expression in the glomeruli was increased in transplant rejection and became detectable in tubules. Expression of NHERF-1 and NHERF-2 was not different in the patient groups. These results indicate that in contrast to the rat, both NHERF isoforms are detected in the human proximal tubule. In renal transplant rejection, there is increased expression of both PDGFR subtypes consistent with a role for PDGF in injury or repair.
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PMID:Expression of NHERF-1, NHERF-2, PDGFR-alpha, and PDGFR-beta in normal human kidneys and in renal transplant rejection. 1286 27

Renal cell carcinoma (RCC) accounts for approximately 3% of all new cancer diagnosis every year. RCC arises from the renal epithelium and represents 85% of all kidney tumors. According to histology, these neoplasms are divided into the following types: clear cell, papillary, chromophobe, oncocytoma, collecting duct, and unclassified. Approximately, 75% of RCCs are of the clear cell type and in recent years, there have been substantial advances in the understanding of its molecular biology leading to the development of effective treatments. However, there is still an area of uncertainty with regard to non-clear cell histologies. Scarce studies have been conducted testing different drugs in this patient population. Thus, most of the evidence comes from small phase II trials, retrospective analysis, or expanded access programs. Recent insights in the molecular basis of these tumors have opened a promising research field. Molecules targeting mammalian target of rapamycin, epidermal growth factor receptor, c-MET, vascular endothelial growth factor, and platelet-derived growth factor are among some of the promising drugs tested in this setting. This article reviews the mechanisms of disease on RCC and summarizes treatment options with a particular focus on patients with non-clear cell tumors.
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PMID:Non-clear cell advanced kidney cancer: is there a gold standard? 2117 5