Differential roles of signaling pathways for proliferation and migration of XXXX pancreatic stellate cells.

@entity32 @entity82 @entity2308 @entity4286 @entity2509 @entity2307 @entity2306 @entity35 @entity4357
Activated pancreatic stellate cells (PSCs) have recently been implicated in the pathogenesis of pancreatic @entity82 and @entity32 . Accumulation of PSCs is a fundamental feature of pancreatic @entity82 , and platelet-derived growth factor (PDGF)-BB is the most potent mitogen for PSCs. But, the molecular mechanisms responsible for PDGF's actions in PSCs are largely unknown. In hepatic stellate cells, it has been established that activation of both @entity4357 (PI) 3-kinase and @entity2509 ( @entity2509 ) pathways is required for PDGF-BB-induced proliferation and migration. The aim of this study was to elucidate the signaling pathways mediating PDGF-BB's actions in PSCs. PSCs were isolated from @entity35 pancreas tissue and used in their culture-activated, myofibroblast-like phenotype. Culture-activated PSCs expressed PDGF alpha- and beta-receptors. PDGF-BB induced autophosphorylation of its receptor, followed by the activation of PI 3-kinase, @entity2308 , and @entity2509 pathways. Activation of PI 3-kinase was not required for PDGF-BB-induced @entity2509 activation. PDGF-BB induced approximately five-fold increase in proliferation and chemotaxis of PSCs. Inhibition of @entity2509 pathway with @entity4286 completely blocked proliferation, whereas @entity4286 had a modest inhibitory effect on cell migration (approximately 50%). On the other hand, inhibition of PI 3-kinase pathway with @entity2307 or @entity2306 almost completely inhibited migration, but did not affect proliferation of PSCs. In conclusion, our results suggest that @entity2509 pathway regulates proliferation and migration in response to PDGF-BB, whereas PI 3-kinase mediates cellular migration, but not proliferation of PSCs.
