Role of transforming growth factor β type II receptor in hepatic fibrosis:: Studies of human chronic hepatitis C and experimental fibrosis in rats

被引:92
作者
Roulot, D
Sevcsik, AM
Coste, T
Strosberg, AD
Marullo, S
机构
[1] Hop Avicenne, Dept Gastroenterol Hepatol, F-93000 Bobigny, France
[2] San Francisco Gen Hosp, Liver Ctr Lab, San Francisco, CA 94110 USA
[3] Inst Cochin Genet Mol, CNRS, UPR 415, Lab Immunopharmacol Mol, F-75014 Paris, France
[4] Inst Cochin Genet Mol, CNRS, UPRES A 1534, Grp Pharmacol Cellulaire & Mol Recepteurs, F-75014 Paris, France
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D O I
10.1002/hep.510290622
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Transforming growth factor beta (TGF-beta) is an antiproliferative and profibrogenic cytokine that signals through a receptor consisting of type I and type II (T beta RII) components. We have examined changes in the expression of T beta RII during liver injury, correlating this with the antiproliferative and profibrogenic effects of TGF-beta(1). The experimental material consisted of biopsy samples of liver from patients with chronic hepatitis C and rats in which liver injury was induced by ligation of the common bile duel. Stellate cells were isolated from normal or injured rat liver and studied as fresh isolates. In the biopsy samples from patients, mRNAs for TGF-beta(1) and T beta RII were measured using competitive reverse polymerase chain reaction (PCR). TGF-beta(1) mRNA was significantly increased in chronic hepatitis C relative to healthy controls (P = .03), while T beta RII mRNA tvas significantly decreased (P = .001). In the rat model, 5 days after bile duct ligation during increased TGF-beta expression, mRNA for T beta RII in stellate cells was 40% of that in stellate cells from control livers. This coincided with increased expression of collagen I mRNA and proliferation of stellate cells. The reciprocal relationship between expression of TGF-beta and the type II receptor suggest ligand-mediated receptor down-regulation. The decreased level of T beta RII appears to be permissive for proliferation while supporting ongoing fibrogenesis, We conclude that modulation of this receptor may be critical to the progression of wound repair in liver.
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页码:1730 / 1738
页数:9
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