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

Transforming growth factor beta (TGF-beta) is an antiproliferative and prof ibrogenic cytokine that signals through a receptor consisting of type I and type II (T beta RII) components. We have examined changes in the expressio n of T beta RII during liver injury, correlating this with the antiprolifer ative and profibrogenic effects of TGF-beta(1). The experimental material c onsisted 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 d uel. Stellate cells were isolated from normal or injured rat liver and stud ied as fresh isolates. In the biopsy samples from patients, mRNAs for TGF-b eta(1) and T beta RII were measured using competitive reverse polymerase ch ain 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 bil e duct ligation during increased TGF-beta expression, mRNA for T beta RII i n stellate cells was 40% of that in stellate cells from control livers. Thi s coincided with increased expression of collagen I mRNA and proliferation of stellate cells. The reciprocal relationship between expression of TGF-be ta and the type II receptor suggest ligand-mediated receptor down-regulatio n. The decreased level of T beta RII appears to be permissive for prolifera tion while supporting ongoing fibrogenesis, We conclude that modulation of this receptor may be critical to the progression of wound repair in liver.