(-)-Epigallocatechin gallate prevents carbon tetrachloride-induced rat hepatic fibrosis by inhibiting the expression of the PDGFRbeta and IGF-1R.

ABSTRACT

Hepatic fibrosis is a major complication of various chronic liver diseases. Activated hepatic stellate cells (HSCs) play a critical role in the development of liver fibrosis and the axis of platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR), a member of receptor tyrosine kinases (RTKs), is closely associated with the activation of HSC. Insulin-like growth factor (IGF)-1 receptor (IGF-1R), which also belongs to RTKs, interacts with the PDGF/PDGFR axis, thereby cooperatively promoting hepatic fibrosis. We herein examined the effects of (-)-epigallocatechin gallate (EGCG), which inhibits the activation of several types of RTKs, on the development of rat liver fibrosis induced by carbon tetrachloride (CCl4). Drinking water with 0.1% EGCG significantly decreased the serum levels of both aspartate aminotransferase and alanine aminotransferase raised by CCl4, thus indicating an improvement of liver injury. In CCl4-injected rats, EGCG markedly attenuated hepatic fibrosis and decreased the amount of hydroxyproline in the experimental liver. The expression of PDGFRbeta and IGF-1R mRNAs in the liver was significantly lowered by the treatment with EGCG. EGCG also decreased the expression of PDGFRbeta and alpha-smooth muscle actin proteins, thus indicating the inhibition of HSC activation. These findings suggest that EGCG can exert, at least in part, an anti-fibrotic effect on the liver by targeting PDGFRbeta and IGF-1R. EGCG might therefore be useful in both the prevention and treatment of hepatic fibrosis.