Role of transforming growth factor-beta in growth and injury response of the pancreatic duct epithelium in vitro

Chronic pancreatitis is characterized by increased levels of expression of transforming growth factor-beta (TGF-beta), particularly in and around the ducts. To examine the consequences of elevated exposure to TGF-beta on the pancreatic duct epithelium, we cultured segments of the main bovine pancrea tic duct in the presence of increasing doses of TGF-beta. We also studied t he effect of TGF-beta on epithelial injury, produced in this model by expos ure to a bile acid. The extent of proliferation, migration, and epithelial damage was measured morphometrically on sections stained with hematoxylin a nd eosin. Proliferation and apoptosis were qualitatively determined by mean s of immunohistochemical analysis. In this model of duct cell culture, TGF- beta stimulated cell migration in areas of the explants where the native ba sement membrane of the duct epithelium was absent;In segments where the nat ive basement membrane remained intact, proliferation was inhibited and apop tosis induced. When the explants were exposed to bile acid, extensive epith elial injury was observed. TGF-beta exposure at high doses (1 nmol/L protec ted epithelial integrity, but cellular morphology was altered and the proce ss of apoptosis appeared to be increased. Our results suggest that increase d periductal levels or TGF-beta in the setting of pancreatic injury may be intended to promote repair of acute epithelial damage but may have detrimen tal long-term effects.