The antifibrotic effect of TGF-beta1 siRNAs in murine model of liver cirrhosis.
Liver fibrosis results from chronic damage to the liver by chronic hepatitis, alcohol, and toxic agents. A characteristic of liver fibrosis is an accumulation of extracellular matrix (ECM) protein, which distorts the hepatic architecture by forming a fibrous scar, and the subsequent development of regenerating nodules defines cirrhosis. Transforming growth factor (TGF)-beta1, one of the most powerful profibrogenic mediators, plays a major role in the development of liver cirrhosis and regulates ECM gene expression and matrix degradation. This study elucidates the changes of TGF-beta1-mediated signals during liver fibrogenesis by using RNA interference. In this experiment, the TGF-beta1 siRNAs reduced the expression of TGF-beta1 in the livers of CCl(4) injection compared with those of control group, and the expression of type I collagen and alpha-smooth muscle actin was decreased. In conclusion, this study demonstrates that TGF-beta1 siRNAs inhibit TGF-beta1 expression in the murine model of liver cirrhosis and might be a good therapeutic strategy to prevent liver cirrhosis in human.
Kim
Kyung-Hyun
KH
Department of Pathology, Catholic University of Daegu, College of Medicine, 3056-6 Daemyung 4-Dong, Nam-Gu, Daegu 705-718, Republic of Korea.
Kim
Hyun-Chul
HC
Hwang
Mee-Yul
MY
Oh
Hoon-Kyu
HK
Lee
Tae-Sung
TS
Chang
Young-Chae
YC
Song
Ho-Jung
HJ
Won
Nam-Hee
NH
Park
Kwan-Kyu
KK
D000199:Actins / Q000378:metabolism; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism / Q000473:pathology; D024042:Collagen Type I / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D053773:Transforming Growth Factor beta1
D000199:Actins; D024042:Collagen Type I; D034741:RNA, Small Interfering; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1