OBJECTIVESTo investigate the dynamic characteristics of Smad anchor for receptor activation (SARA) expression during liver fibrogenesis in rats and the relationship between SARA and liver fibrosis.

METHODSLiver fibrosis was induced in 74 rats by intraperitoneal injection of dimethylnitrosamine (DMN) with a dosage of 10 microl/kg body weight, once a day, 3 days per week for 4 weeks. The model rats were randomly divided into 9 groups for studying the changes: 1 d, 3 ds, 1 week, 2 weeks, 3 weeks and 4 weeks after starting the ip injections (intoxicating phase), and 1 week, 2 weeks and 4 weeks after stopping the injections (5th w, 7th w and 8th w, recovery phase). Each group included 5 to 8 rats. In addition, 10 non-treated rats served as normal controls. The rat liver tissues were examined. Collagen deposition was stained with Sirius red, and hydroxyproline (Hyp) was measured with Jamall' method. SARA spatial expression in the livers was detected by immunohistochemistry, and the expressions of TGFbeta1, alpha-SMA and SARA protein were detected by Western blot. The relationships of SARA with Hyp, TGFbeta1 and alpha-SMA were analyzed.

RESULTSDuring the intoxicating phase, the rat hepatic collagen production (Hyp content) and deposition increased as DMN intoxication continued, and there was marked fibrous septum and pseudo-lobule formation at the end of the 4th w. During the recovery phase, the rat hepatic collagen deposition and fibrous septum formation were lessened, but the Hyp content in the livers of the model rats at the end of 4th w, 5th w, 6th w and 8th w was still higher than that of the controls (193.04+/-39.15, 188.49+/-39.92, 174.39+/-21.22, 163.59+/-31.47 vs 125.64+/-19.51; t from 3.43 to 4.9, P<0.01). SARA was mainly stained positively in interstitial cells surrounding the hepatic sinusoids in both normal and fibrotic livers, and the number of the positive stained cells decreased as liver fibrosis developed, and gradually returned to normal after stopping the intoxication. The expressions of TGFbeta1 and alpha-SMA were gradually increased, as shown with Western blot, but SARA decreased as liver fibrosis developed. The expressions of TGFbeta1 and alpha-SMA were slightly decreased, SARA expression recovered to the normal level after stopping the DMN intoxication. During liver fibrosis developing and recovery phases, SARA was significantly negatively correlated with TGFbeta1 and alpha-SMA expressions and Hyp contents.

CONCLUSIONSSARA was mainly expressed in the liver interstitial cells, and it was negatively correlated with liver fibrosis formation.