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 pancreatic duct in the presence of increasing doses of TGF-beta. We also studied the effect of TGF-beta on epithelial injury, produced in this model by exposure to a bile acid. The extent of proliferation, migration, and epithelial damage was measured morphometrically on sections stained with hematoxylin and eosin. Proliferation and apoptosis were qualitatively determined by means of immunohistochemical analysis. In this model of duct cell culture, TGF-beta stimulated cell migration in areas of the explants where the native basement membrane of the duct epithelium was absent;In segments where the native basement membrane remained intact, proliferation was inhibited and apoptosis induced. When the explants were exposed to bile acid, extensive epithelial injury was observed. TGF-beta exposure at high doses (1 nmol/L protected epithelial integrity, but cellular morphology was altered and the process of apoptosis appeared to be increased. Our results suggest that increased periductal levels or TGF-beta in the setting of pancreatic injury may be intended to promote repair of acute epithelial damage but may have detrimental long-term effects.