Molecular mechanisms of pancreatitis: current opinion.
Pancreatitis (necroinflammation of the pancreas) has both acute and chronic manifestations. Gallstones are the major cause of acute pancreatitis, whereas alcohol is associated with acute as well as chronic forms of the disease. Cases of true idiopathic pancreatitis are steadily diminishing as more genetic causes of the disease are discovered. The pathogenesis of acute pancreatitis has been extensively investigated over the past four decades; the general current consensus is that the injury is initiated within pancreatic acinar cells subsequent to premature intracellular activation of digestive enzymes. Repeated attacks of acute pancreatitis have the potential to evolve into chronic disease characterized by fibrosis and loss of pancreatic function. Our knowledge of the process of scarring has advanced considerably with the isolation and study of pancreatic stellate cells, now established as the key cells in pancreatic fibrogenesis. The present review summarizes recent developments in the field particularly with respect to the progress made in unraveling the molecular mechanisms of acute and chronic pancreatic injury secondary to gallstones, alcohol and genetic factors. It is anticipated that continued research in the area will lead to the identification and characterization of molecular pathways that may be therapeutically targeted to prevent/inhibit the initiation and progression of the disease.
Pancreatic Research Group, South Western Sydney Clinical School, Liverpool Hospital and The University of New South Wales, Sydney, Australia.
Alain
A
Vonlaufen
Jeremy S
JS
Wilson
Minoti V
MV
Apte
D000208:Acute Disease; D000428:Alcohol Drinking / Q000009:adverse effects; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000473:pathology; D018450:Disease Progression; D000431:Ethanol / Q000009:adverse effects / Q000378:metabolism; D005355:Fibrosis; D042882:Gallstones / Q000150:complications; D020022:Genetic Predisposition to Disease; D006801:Humans; D010179:Pancreas / Q000201:enzymology / Q000473:pathology*; D010195:Pancreatitis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D019512:Pancreatitis, Alcoholic / Q000209:etiology / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D012307:Risk Factors
D000431:Ethanol