Transforming growth factor-β-induced upregulation of transforming growth factor-β receptor expression in pancreatic regeneration

The transforming growth factor-beta (TGF beta) signaling pathway is one important player in the regulation of extracellular matrix turnover and cell proliferation in epithelial regeneration. We used cerulein-induced pancreatitis in rats as a model to investigate the regulation of TGF beta receptor type I and type II expression on protein and messenger RNA level during regeneration. In the regenerating pancreas, mRNA levels of TGF beta receptor I and II were significantly increased with a maximum after 2 days. On protein level, expression of TGF beta receptor II was significantly increased after 3-5 days. This elevated expression could be inhibited by neutralizing the endogenous biological activity of TGF beta(1) with a specific antibody. In cultured pancreatic epithelial cells, TGF beta(1) reduced cell proliferation as measured by [H-3]thymidine incorporation. Furthermore the transcript levels of TGF beta(1) as well as mRNA and protein concentrations of type I and type II receptor increased during TGF beta stimulation in vitro. These results indicate that epithelial pancreatic cells contribute to the enhanced TGF beta(1) synthesis during pancreatic regeneration by an autocrine mechanism. TGF beta(1), furthermore, upregulates the expression of its own receptors during the regenerative process, thereby contributing to the increase of the TGF beta-induced cellular responses. (C) 1999 Published by Elsevier Science B.V. All rights reserved.