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J Gastroenterol Hepatol. 2008 Mar;23 Suppl 1:S119-21. doi: 10.1111/j.1440-1746.2007.05296.x.

Pancreatic stellate cells: molecular mechanism of pancreatic fibrosis.

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  • 1Institute of Gastroenterology, Department of Medicine, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan. kyoko@ige.twmu.ac.jp

Abstract

Pancreatic stellate cells (PSC) are known to play a crucial role in pancreatic fibrogenesis in chronic pancreatitis and in the desmoplastic reaction of pancreatic cancer. When PSC are stimulated by oxidative stress, the phenotype of quiescent fat-storing cells converts to myofibroblast-like activated PSC that then produce extracellular matrix (ECM), adhesion molecules, and various chemokines in response to inflammatory cytokines, chemokines, and growth factors. Platelet-derived growth factor (PDGF) is a potent stimulator of PSC proliferation, and transforming growth factor-beta, PDGF, and basic fibroblast growth factor stimulate ECM synthesis by PSC. As induction of acinar cell apoptosis and necrosis is a major mechanism in the pathogenesis of mild to severe acute pancreatitis, the rapid removal of apoptotic acinar cells may be helpful in preventing the release of toxic intracellular materials, preventing further progression of the inflammation, and restoring normal tissue homeostasis. Although PSC are not professional phagocytes, we have demonstrated that PSC engulf apoptotic polymorphonuclear neutrophils (PMN) and necrotic acinar cells. Apoptotic PMN are ingested into the cytoplasm of the PSC, and troglitazone induces a dose-dependent increase in both phagocytic activity and expression of CD36, which is a representative scavenger receptor for phagocytic function. Engulfment of necrotic acinar cells by PSC induced PSC death and inhibited PSC activation in an in vitro study, suggesting that engulfment of necrotic acinar cells by PSC may inhibit the progression of fibrogenesis. These findings suggest that engulfment of damaged cells by PSC may be one of the mechanisms that prevent the progression of pancreatitis and restore tissue homeostasis.

PMID:
18336654
[PubMed - indexed for MEDLINE]
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