title: (-)-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.
authors: Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors: Yoichi
authors: Y
authors: Yasuda
authors: Masahito
authors: M
authors: Shimizu
authors: Hiroyasu
authors: H
authors: Sakai
authors: Junpei
authors: J
authors: Iwasa
authors: Masaya
authors: M
authors: Kubota
authors: Seiji
authors: S
authors: Adachi
authors: Yosuke
authors: Y
authors: Osawa
authors: Hisashi
authors: H
authors: Tsurumi
authors: Yukihiko
authors: Y
authors: Hara
authors: Hisataka
authors: H
authors: Moriwaki
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002251:Carbon Tetrachloride; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D000410:Alanine Transaminase; D016588:Anticarcinogenic Agents; D001219:Aspartate Aminotransferases; D002251:Carbon Tetrachloride; D002392:Catechin; D012333:RNA, Messenger; D017526:Receptor, IGF Type 1; D020797:Receptor, Platelet-Derived Growth Factor beta; C498862:Acta2 protein, rat; C045651:epigallocatechin gallate