Extracellular matrix is reduced by inhibition of transforming growth factor beta1 in pancreatitis in the rat.
OBJECTIVE
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.
Menke
A
A
Internal Medicine I. University of Ulm, Germany. andre.menke@medizin.uni-ulm.de
Yamaguchi
H
H
Gress
T M
TM
Adler
G
G
D000208:Acute Disease; D000818:Animals; D015153:Blotting, Western; D002108:Ceruletide; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000378:metabolism / Q000502:physiology*; D010195:Pancreatitis / Q000139:chemically induced / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*
D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D002108:Ceruletide; D003094:Collagen