TGFβ1 autocrine growth control in isolated pancreatic fibroblastoid cells/stellate cells in vitro

TGF beta 1 is a multifunctional factor, controlling cellular growth and extracellular matrix production. Deletion of the TGF beta 1 gene in mice results 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 primary candidates for production and deposition of extracellular matrix. Still, little is known about regulation of these cells during development of pancreatic disease. We established primary cell lines of pancreatic fibroblastoid/stellate cells (PFC) from rat pancreas. Investigation of rPFCs in vitro shows TGF beta 1 expression by RT-PCR analysis. Mature TGF beta 1 was detected 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 neutralizing antibodies interferes with an autocrine loop and results in a 2-fold stimulation 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 of 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 growth control of pancreatic fibroblastoid cells. (C) 2000 Elsevier Science B.V. All rights reserved.