Extracellular matrix is reduced by inhibition of transforming growth factor beta 1 in pancreatitis in the rat

Background & Aims: Regeneration from cerulein-induced pancreatitis is accompanied by a transient synthesis and deposition of extracellular matrix components in the rat pancreas. The pleiotropic transforming growth factor (TGF)-beta 1 has been suggested to regulate extracellular matrix remodeling during regeneration from acute pancreatitis. The present study was designed to verify this hypothesis by investigating the effect of TGF-beta 1 inhibition. Methods: Experimental acute pancreatitis was induced in vats by supramaximal doses of cerulein. The biological activity of TGF-beta 1 was inhibited by injections of neutralizing TGF-beta 1 antibody. Changes in the content of extracellular matrix proteins, TGFs, and their messenger RNA concentrations weve monitored. Results: TGF-beta 1 expression in pancreatic cells was suppressed after induction of acute pancreatitis by the application of neutralizing TGF-beta 1 antibody. Immunochemical analysis showed a clear reduction of extracellular matrix formation during the regeneration of the pancreas in antibody-treated animals. The hydroxyproline content and the concentration of collagen types I and III, fibronectin on protein, and messenger RNA level were significantly reduced in the pancreas of treated animals. Conclusions: These results provide evidence that TGF-beta 1 is involved in the regulation of extracellular matrix remodeling in the rat pancreas during regeneration from acute pancreatitis.