Repetitive self-limited acute pancreatitis induces pancreatic fibrogenesisin the mouse

The role of repetitive acute injury in the pathogenesis of chronic pancreat itis remains unknown. To determine if repetitive injury induced by pancreat ic hyperstimulation would reproduce the characteristic features of human ch ronic pancreatitis, acute reversible pancreatic injury was induced in mice by twice weekly cerulein treatment, 50 ug/kg/hr x 6 hr, for 10 weeks. Proco llagen alpha 1(I) mRNA was markedly increased by week 2. Sirius red stainin g of interstitial collagen demonstrated progressive accumulation of extrace llular matrix surrounding acinar units and in interlobular spaces. Atrophy, transdifferentiation of acinar units to ductlike tubular complexes, and di latation of intraacinar lumina also developed. Electron microscopy demonstr ated the presence of stromal cells in areas of fibrosis with morphologic ch aracteristics of pancreatic stellate cells. These findings demonstrate that , in a murine model, repetitive acute injury to the pancreas by hyperstimul ation can reproduce the major morphological characteristics of human chroni c pancreatitis.