TGF beta 1 autocrine growth control in isolated pancreatic fibroblastoid cells/stellate cells in vitro

TGF beta 1 is a multifunctional factor, controlling cellular growth and ext racellular matrix production. Deletion of the TGF beta 1 gene in mice resul ts in multiple; inflammatory reactions. Targeted overexpression of TGF beta 1 in pancreatic islet cells leads to fibrosis of the exocrine pancreas in transgenic mice. In pancreatic fibrosis interstitial fibroblasts are primar y candidates for production and deposition of extracellular matrix. Still, little is known about regulation of these cells during development of pancr eatic disease. We established primary cell lines of pancreatic fibroblastoi d/stellate cells (PFC) from rat pancreas. Investigation of rPFCs in vitro s hows TGF beta 1 expression by RT-PCR analysis. Mature TGF beta 1 was detect ed in culture supernatants by immunoassay. Rat PFCs in culture possess both receptors TGF beta receptor type I, and type II, necessary for TGF beta 1 signal transduction. Inhibition of TGF beta 1 activity by means of neutrali zing antibodies interferes with an autocrine loop and results in a 2-fold s timulation of cell growth. So far, pancreatic fibroblastoid/stellate cells in vitro were known as a target of TGF beta 1 action, but not as a source o f TGF beta 1. Our data indicate TGF beta 1 activity in rat pancreas extends beyond regulation of matrix production, but appears to be important in gro wth control of pancreatic fibroblastoid cells. (C) 2000 Elsevier Science B. V. All rights reserved.