Effects of pancreatic secretory stress proteins (SSP) on human pancreatic stellate cells (hPSC)
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Pancreatic stellate cells (PSC) play a central role in fibrogenesis associated with acute and chronic pancreatitis. PSC produce the majority of collagen types I and III (coll-1, coll-3) and fibronectin (FN), but contribute also to remodeling by secreting MMPs. Pancreatic stone protein/regenerating protein (PSP/reg) and pancreatitis-associated protein (PAP) belong to a family of secretory stress proteins (SSP) synthesized in acinar cells. SSP are dramatically increased during acute and chronic pancreatitis. Assuming a protective role of these stress proteins we investigated their effects on human PSC. SSP were expressed in the yeast Pichia pastoris and purified from medium supernatants. Human PSC were obtained by outgrowth from fibrotic human pancreas tissue. SSP were added at concentrations of 10, 30 and 100ng/ml to cultured PSC. Cell proliferation was determined by BrdU incorporation. PSC migration was assessed by the wound-assay. Matrix synthesis was measured by immunoassay of coll-1 and FN in PSC supernatants and cell associated collagens and FN were detected by immunofluorescence microscopy. MMPs were demonstrated by zymography, Western-analysis, immunoassay and rt-PCR. TIMP-1 and -2 were detected by Western-blot. Our data provide evidence in vitro that SSP may reduce pancreatic fibrosis and might stimulate pancreatic fibrolysis. By inhibiting PSC activation (reduce PSC proliferation and matrix synthesis, respectively), SSP may diminish the activated PSC numbers and reduce ECM accumulation; and by decreasing TIMPs more effective than MMPs, ECM degradation is promoted. Therefore, SSP might act as antifibrogenic proteins in pancreatic injury.
Subject HeadingsBauchspeicheldrüsenentzündung [GND]
Pancreatitis, acute necrotizing [MeSH]