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

The collecting duct system of the metanephric kidney develops from the ureteric bud, an outgrowth from the caudal end of the Wolffian duct. The ureteric bud is induced to form by signals emanating from a specific area of intermediate mesoderm, which it immediately invades. In response to further mesenchyme-derived signals, the ureteric bud ramifies to form a tree-like collecting duct system, which in turn signals clumps of the mesenchyme cells that surround it to differentiate into epithelial nephrons. The morphogenesis of the collecting duct system is driven by two processes--growth and branching--which are to some extent separable. Each depends on diffusible signals, a number of which have been identified in recent years; growth promoters include hepatocyte growth factor and activin, while ramogens include glial cell line-derived neurotrophic factor, neurturin and persephin. Arborisation also depends on matrix components, including proteoglycans, integrins and their ligands, and metalloproteinases, such as matrix metalloproteinase-9, that are involved in matrix remodelling. So far, little progress has been made in elucidating the intracellular pathways responsible for translating growth factor "instructions" into morphological change, but a role for some intracellular components, such as protein kinase C, formins and the cytoskeleton, is implied by recent experimental data. More information on these internal pathways of control is expected over the next few years.
 ...
PMID:Collecting duct morphogenesis. 1045 85

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.
 ...
PMID:Intracellular and extracellular regulation of ureteric bud morphogenesis. 1132 19

Bone morphogenetic protein (BMP)-7 exerts dose-dependent stimulatory and inhibitory effects during renal branching morphogenesis. Previously, we identified an inhibitory role for activin-like kinase receptors and Smad1 in BMP-dependent inhibition (Piscione, T. D., Phan, T., and Rosenblum, N. D. (2001) Am. J. Physiol. 280, F19-F33). Here we demonstrate a novel role for p38 mitogen-activated kinase (p38(MAPK)) in BMP7-dependent stimulatory signaling. Stimulatory doses (0.25 nm) of BMP7 increased p38(MAPK) activity and stimulated phosphorylation of endogenous activating transcription factor 2 (ATF2) in a p38(MAPK)-dependent manner in murine inner medullary collecting duct (mIMCD-3) cells. In contrast, high doses (10 nm) of BMP7 inhibited p38(MAPK) activity and phosphorylation of endogenous ATF2. Treatment with BMP7 exerted no significant effect on the levels of the phosphorylated forms of endogenous SAPK/JNK or p44 and p42 (ERK1 and ERK2) protein kinases. To investigate the functional importance of p38(MAPK) signaling, we showed that SB203580, a p38(MAPK) inhibitor, blocked the stimulatory effect of BMP7 on mIMCD-3 cell morphogenesis but had no effect on BMP7-dependent inhibition in a three-dimensional culture model. To identify mechanisms by which BMP7-dependent inhibitory signaling suppresses p38(MAPK) activity, we measured p38(MAPK) activity in ligand independent mIMCD-3 models of enhanced and suppressed Smad signaling. Basal activity of p38(MAPK) was decreased in mIMCD-3 cells and in embryonic kidney tissue expressing a constitutively active activin-like kinase receptor, but was increased in mIMCD-3 cells stably expressing a dominant negative form of Smad1. We conclude that BMP7 stimulates renal epithelial cell morphogenesis via p38(MAPK) and that p38(MAPK) activity is negatively regulated by Smad1.
 ...
PMID:p38MAPK acts in the BMP7-dependent stimulatory pathway during epithelial cell morphogenesis and is regulated by Smad1. 1471 43