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)

Bone morphogenetic protein (BMP)-2 and hepatocyte growth factor (HGF) exert antagonistic effects on renal collecting duct formation during embryogenesis. A current model proposes HGF inhibits BMP-2 signaling at the level of Smad1 in a common target cell. Here, we show that BMP-2 and HGF control collecting duct formation via parallel pathways. We examined the interactions between BMP-2 and HGF in the mIMCD-3 model of collecting duct morphogenesis. During tubule formation, HGF rescued the inhibitory effects of BMP-2 and of a constitutive active form of the BMP-2 receptor, ALK3, stably expressed in mIMCD-3 cells. To determine whether the effect of HGF occurs through known mediators which act downstream of the BMP-2/ALK3 complex, we examined the effect of HGF on BMP-2-induced Smad1 phosphorylation, Smad1/Smad4 complex formation, and Smad1 nuclear translocation. Neither HGF nor other receptor tyrosine kinase ligands (EGF, FGF-4) induced phosphorylation of endogenous Smad1 in mIMCD-3 cells or in Mv1Lu, MC3T3-E1 or P19 cells. Furthermore, none of these ligands blocked induction of the BMP-responsive promoter, Tlx2. Thus, HGF overcomes the inhibitory effects of BMP-2 on collecting duct morphogenesis without interrupting any of the known signaling events in the BMP-2 dependent Smad1 signaling pathway. We conclude that BMP-2/ALK3 and HGF function to control parallel pathways downstream of their respective cell surface receptors. Integration of these signals likely occurs at the level of transcriptional or post-transcriptional events.
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PMID:BMP-2/ALK3 and HGF signal in parallel to regulate renal collecting duct morphogenesis. 1063 78

The renal connecting tubule (CNT) is a distinct segment that occurs between the distal convoluted tubule (DCT) and the cortical collecting duct. On the basis of its characterization in rabbit it is widely believed that connecting tubule cells have a low permeability to water and do not respond to vasopressin. Here we utilize segment-specific markers and specific aquaporin antibodies to characterize expression of water channels in CNT of the rat by immunocytochemistry. Colocalization of aquaporin 2 (AQP2), AQP3, and AQP4 with Na(+), Ca(2+) exchanger (NCX), a transporter characteristic of the connecting tubule, gave heterogeneous labeling. There was aquaporin labeling in many but not all regions labeled by NCX. Colocalization of AQP2 with AQP3 and with AQP4 showed that AQP3 and AQP4 labeling were always accompanied by AQP2. Immunogold labeling and electron microscopy showed that NCX-labeled cells with AQP2 labeling had the morphology of CNT cells, whereas NCX-labeled cells without AQP2 labeling were DCT cells. The latter regions were identified as the late region of the DCT known as DCT2. Additionally, regions of CNT lacking AQP2 labeling could be identified in Brattleboro rats not treated with vasopressin but not in such animals chronically treated with deamino-Cys(1),D-Arg(8)-vasopressin (dDAVP). Quantitative analysis of labeling was consistent with expression of AQP2 over a longer region of CNT after dDAVP exposure.
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PMID:Expression of aquaporins in the renal connecting tubule. 1105 48

The organization of Na(+) and Ca(2+) transport pathways along the mouse distal nephron is incompletely known. We revealed by immunohistochemistry a set of Ca(2+) and Na(+) transport proteins along the mouse distal convolution. The thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC) characterized the distal convoluted tubule (DCT). The amiloride-sensitive epithelial Na(+) channel (ENaC) colocalized with NCC in late DCT (DCT2) and extended to the downstream connecting tubule (CNT) and collecting duct (CD). In early DCT (DCT1), the basolateral Ca(2+)-extruding proteins [Na(+)/Ca(2+) exchanger (NCX), plasma membrane Ca(2+)-ATPase (PCMA)] and the cytoplasmic Ca(2+)-binding protein calbindin D(28K) (CB) were found at very low levels, whereas the cytoplasmic Ca(2+)/Mg(2+)-binding protein parvalbumin was highly abundant. NCX, PMCA, and CB prevailed in DCT2 and CNT, where we located the apical epithelial Ca(2+) channel (ECaC1). Its subcellular localization changed from apical in DCT2 to exclusively cytoplasmic at the end of CNT. NCX and PMCA decreased in parallel with the fading of ECaC1 in the apical membrane. All three of them were undetectable in CD. These findings disclose DCT2 and CNT as major sites for transcellular Ca(2+) transport in the mouse distal nephron. Cellular colocalization of Ca(2+) and Na(+) transport pathways suggests their mutual interactions in transport regulation.
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PMID:Distribution of transcellular calcium and sodium transport pathways along mouse distal nephron. 1170 51