Pancreatic stellate cell migration: role of the phosphatidylinositol 3-kinase (PI3-kinase) pathway

摘要: Pancreatic stellate cells (PSCs) are implicated as key mediators of pancreatic fibrogenesis and found in increased numbers areas injury. This increase number may be due to local proliferation and/or migration PSCs affected from surrounding tissue. We have recently shown that can migrate this is stimulated by PDGF a predominantly chemotactic manner [Gut 52 (2003) 677]. However, the signalling mechanisms responsible for PDGF-induced PSC not known. Aims: (i) To determine whether mediated PI3-kinase pathway. (ii) investigate cell influenced an interaction exists between pathway ERK1/2 (known mediate proliferation) exposed PDGF. Methods: activity was assessed measuring activation (phosphorylation) its downstream substrate Akt rat incubated with (10 ng/mL) 5 min, 15 60 24 hr presence or absence specific inhibitor wortmannin. The role examined assessing through porous membrane after exposure wortmannin hr. (iii) relationship examining mitomycin C, proliferation. (iv) incubation wortmannin, followed assessment western blot. Results: early at min sustained Inhibition decreased basal well also inhibited activation. C significantly reduced (but did abolish) migration. Conclusions: induced induction least plays partially involved mediating dependent, part, on