Battle-scarred pancreas: role of alcohol and pancreatic stellate cells in pancreatic fibrosis.
Pancreatic stellate cells (PSC) are now recognized as the key mediators of pancreatic fibrosis, a characteristic feature of chronic pancreatitis. The role of PSC in alcoholic pancreatic fibrosis has been examined in vivo (using pancreatic tissue from patients with alcohol-induced chronic pancreatitis and from animal models of experimental pancreatitis) and in vitro (using PSC in culture). These studies indicate that PSC are activated early in the course of pancreatic injury and are the predominant source of collagen in the fibrotic pancreas. The factors responsible for mediating PSC activation during chronic alcohol exposure include ethanol, its metabolite acetaldehyde, oxidant stress and cytokines (released during episodes of alcohol-induced pancreatic necroinflammation). Most recently, the intracellular signaling mechanisms regulating ethanol-induced PSC activation have been identified and include the mitogen-activated protein kinase (MAPK) pathway, phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), and the transcription factor activator protein-1 (AP-1).
Apte
Minoti V
MV
Pancreatic Research Group, South-western Sydney Clinical School, Liverpool Hospital, Sydney, Australia. m.apte@unsw.edu.au
Pirola
Romano C
RC
Wilson
Jeremy S
JS
D000079:Acetaldehyde / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D018384:Oxidative Stress; D010179:Pancreas / Q000166:cytology* / Q000473:pathology; D019512:Pancreatitis, Alcoholic / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism
D004791:Enzyme Inhibitors; D018808:Transcription Factor AP-1; D000431:Ethanol; D011494:Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000079:Acetaldehyde