Prevention of fibrosis in experimental colitis by captopril: the role of tgf-beta1.
OBJECTIVE
There is a body of evidence to suggest that the local activation of angiotensin II (ANG II) plays a pivotal role in fibrogenic response involving the kidney, heart, lung, pancreas and liver. In such conditions, fibrosis is mediated, at least partially, through ANG II induction of the cytokine transforming growth factor-beta1 (TGF-beta1). Both ANG II and TGF-beta1 also seem to be involved in intestinal fibrosis and stenosis, particularly in Crohn's disease. The aim of the present study was, firstly, to determine the effects of the angiotensin-converting enzyme inhibitor, captopril, on colonic fibrosis in experimental colitis in rats and, secondly, to check the role of TGF-beta1 on these effects.


METHODS
Colitis was induced in rats by intracolonic administration of TNBS. Colonic fibrosis was assessed 21 days later by macroscopic and microscopic evaluation. Levels of collagen alpha1 gene expression, hydroxyproline, angiotensin II and TGF-beta1 proteins, and TGF-beta1 mRNA were measured on the colonic tissue.


RESULTS
In chronic colitis, captopril significantly reduced the score of macroscopic and histologic lesions, as well as the colonic tissue levels of collagen alpha1, hydroxyproline, ANG II and TGF-beta1 proteins, and TGF-beta1 mRNA.


CONCLUSIONS
These data demonstrate for the first time that the prophylactic administration of captopril is effective in preventing colonic fibrosis in TNBS-induced colitis. The antifibrotic action of captopril could be due to the blockade of TGFbeta-1 overexpression, and/or to a direct down-regulation of TGFbeta-1 transcript.
Wengrower
Dov
D
Department of Gastroenterology, Hadassah University Hospital, Hebrew University Medical School, Jerusalem, Israel.
Zanninelli
Giuliana
G
Zannineli
Giuliana
G
Pappo
Orit
O
Latella
Giovanni
G
Sestieri
Mirna
M
Villanova
Amancay
A
Faitelson
Yoram
Y
Pines
Mark
M
Goldin
Eran
E
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000473:pathology*; D004195:Disease Models, Animal; D005355:Fibrosis / Q000517:prevention & control; D008297:Male; D051381:Rats; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1
D000806:Angiotensin-Converting Enzyme Inhibitors; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D002216:Captopril