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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular mechanisms that control renal development are largely undefined. The discovery of mutations in the gene encoding glypican-3 (Gpc3) in humans with Simpson-Golabi-Behmel syndrome (SGBS) and renal dysplasia, and the establishment of a genetic mouse model of GPC3 deficiency has provided an opportunity to define the role of GPC3 during renal development. Glypicans are a family of cell surface heparan sulfate proteoglycans that control growth factor signalling in nonrenal tissues. Mutational inactivation of Gpc3 causes somatic overgrowth and cystic renal dysplasia, as observed in SGBS. Overgrowth of the ureteric bud and its branches and increased ureteric bud cell proliferation is observed during the early stages of renal development. Subsequently, during corticomedullary differentiation, cortical collecting duct cell proliferation is increased, while medullary collecting duct cells proliferate at a reduced rate and undergo apoptosis resulting in degeneration of the medulla. However, cells that constitute medullary cysts are characterized by enhanced cell proliferation and a lower rate of apoptosis. Thus, the phenotype arising from Gpc3 inactivation demonstrates that tight regulation of cell proliferation and apoptosis is critical during formation of the renal medulla.
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PMID:Glypicans and the biology of renal malformations. 1132 81

The glypican (Gpc) family of cell surface heparan sulfate proteoglycans are expressed in a tissue-specific and developmentally regulated fashion. To determine if individual Gpcs can modulate heparin-binding growth factor signaling, we examined hepatocyte growth factor (HGF)-stimulated mitogenic, motogenic, and morphogenic responses of renal tubular cells expressing different Gpcs. Adult inner medullary collecting duct (IMCD) cells were found to express primarily Gpc4 and to proliferate, migrate, and form tubules with HGF, correlating with sustained extracellular signal-regulated kinase (ERK) activation. Embryonic IMCD cells expressing predominantly Gpc3 proliferated and migrated in response to HGF but activated ERK only transiently and failed to form tubules. Overexpressing Gpc-4 but not Gpc-3 or Gpc-1 led to sustained HGF-stimulated ERK activation and rescued the tubulogenic response in these cells. These results demonstrate that both signaling and phenotypic responses to HGF can be regulated by specific Gpc expression patterns.
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PMID:Hepatocyte growth factor-mediated renal epithelial branching morphogenesis is regulated by glypican-4 expression. 1536 91