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)-beta1 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-beta1 inhibition. METHODS: Experimental acute pancreatitis was induced in rats by supramaximal doses of cerulein. The biological activity of TGF-beta1 was inhibited by injections of neutralizing TGF-beta1 antibody. Changes in the content of extracellular matrix proteins, TGFs, and their messenger RNA concentrations were monitored. RESULTS: TGF-beta1 expression in pancreatic cells was suppressed after induction of acute pancreatitis by the application of neutralizing TGF-beta1 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-beta1 is involved in the regulation of extracellular matrix remodeling in the rat pancreas during regeneration from acute pancreatitis.
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)-beta1 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-beta1 inhibition. METHODS: Experimental acute pancreatitis was induced in rats by supramaximal doses of cerulein. The biological activity of TGF-beta1 was inhibited by injections of neutralizing TGF-beta1 antibody. Changes in the content of extracellular matrix proteins, TGFs, and their messenger RNA concentrations were monitored. RESULTS:TGF-beta1 expression in pancreatic cells was suppressed after induction of acute pancreatitis by the application of neutralizing TGF-beta1 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-beta1 is involved in the regulation of extracellular matrix remodeling in the rat pancreas during regeneration from acute pancreatitis.
Authors: M V Apte; P S Haber; S J Darby; S C Rodgers; G W McCaughan; M A Korsten; R C Pirola; J S Wilson Journal: Gut Date: 1999-04 Impact factor: 23.059
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Authors: A Schmid-Kotsas; H J Gross; A Menke; H Weidenbach; G Adler; M Siech; H Beger; A Grünert; M G Bachem Journal: Am J Pathol Date: 1999-11 Impact factor: 4.307
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