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Selective Inhibition of Activated Stellate Cells and Protection from Carbon Tetrachloride-Induced Liver Injury in Rats by a New PPAR${gamma}$ agonist KR62776
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  • Selective Inhibition of Activated Stellate Cells and Protection from Carbon Tetrachloride-Induced Liver Injury in Rats by a New PPAR${gamma}$ agonist KR62776
저자명
Bae. Myung-Ae,Rhee. Sang-Dal,Jung. Won-Hoon,Ahn. Jin-Hee,Song. Byoung-Joon,Cheon. Hyae-Gyeong
간행물명
Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea
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2010년|33권 3호|pp.433-442 (10 pages)
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

Activated hepatic stellate cells (HSC) are the primary source of extracellular matrix proteins found in liver fibrosis/cirrhosis patients. Therefore, the prevention of HSC activation is an important strategy for treating severe liver injury. This study examined the effects of KR62776, a new peroxisome proliferator-activated receptor ${gamma}$ (PPAR${gamma}$) agonist, on the rate of cell proliferation and expression of ${alpha}$-smooth muscle actin (${alpha}$-SMA) in rat hepatic stellate HSC-T6 cells. In addition, its effects on the liver damage induced by carbon tetrachloride were investigated. KR62776 caused the apoptosis of activated HSC-T6 cells with the concomitant decrease in the ${alpha}$-smooth muscle actin levels in a time- and concentration-dependent manner. However, KR62776 did not cause the apoptosis of human HepG2 and rat McARH7777 hepatoma cells, suggesting that KR62776 has a specific effect on stellate cells. KR62776 increased the levels of Gadd45, p27, p21 and PPAR${gamma}$ proteins but decreased the cell cyclerelated proteins, such as cdk2, cyclin B and cyclin D1. These changes were reversed by BADGE, a specific PPAR${gamma}$ antagonist, indicating that the effects of KR62776 are, at least in part, PPAR${gamma}$-dependent. In addition, KR62776 administration showed some protection against carbon tetrachloride-induced hepatocellular damage in rats. Overall, these results suggest that KR62776 may have potential in the chemoprevention of liver fibrosis/cirrhosis.