The transforming growth factor-β (TGFβ) 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 TGFβ receptor type I and type II expression on protein and messenger RNA level during regeneration. In the regenerating pancreas, mRNA levels of TGFβ receptor I and II were significantly increased with a maximum after 2 days. On protein level, expression of TGFβ receptor II was significantly increased after 3-5 days. This elevated expression could be inhibited by neutralizing the endogenous biological activity of TGFβ1 with a specific antibody. In cultured pancreatic epithelial cells, TGFβ1 reduced cell proliferation as measured by [3H]thymidine incorporation. Furthermore the transcript levels of TGFβ1 as well as mRNA and protein concentrations of type I and type II receptor increased during TGFβ stimulation in vitro. These results indicate that epithelial pancreatic cells contribute to the enhanced TGFβ1 synthesis during pancreatic regeneration by an autocrine mechanism. TGFβ1, furthermore, upregulates the expression of its own receptors during the regenerative process, thereby contributing to the increase of the TGFβ-induced cellular responses. Copyright (C) 1999.
Menke, A., Geerling, I., Giehl, K., Vogelmann, R., Reinshagen, M., & Adler, G. (1999). Transforming growth factor-β-induced upregulation of transforming growth factor-β receptor expression in pancreatic regeneration. Biochimica et Biophysica Acta - Molecular Cell Research, 1449(2), 178–185. https://doi.org/10.1016/S0167-4889(99)00011-7