¦Â-Catenin pathway is required for TGF-¦Â1 inhibition of PPAR¦Ã expression in cultured hepatic stellate cells

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• 作者：Jingjing Qian ; Minghui Niu ; Xuguang Zhai ; Qian Zhou ; Yajun Zhou
• 关键词：TGF-¦Â1 ; transforming growth factor-¦Â1 ; PPAR¦Ã ; peroxisome proliferator-activated receptor-¦Ã ; GSK-3¦Â ; glycogen synthase kinase-3¦Â ; ECM ; extracellular matrix proteins ; HSC ; hepatic stellate cell ; ERK1/2 ; extracellular regulated protein kinase1/2 ; TIMP
• 刊名：Pharmacological Research
• 出版年：2012
• 出版时间：September, 2012
• 年：2012
• 卷：66
• 期：3
• 页码：219-225
• 全文大小：655 K

文摘

Hepatic stellate cell (HSC) activation is a key step in process of liver fibrosis. Transforming growth factor-¦Â1 (TGF-¦Â1) is the most powerful mediator of HSC activation and plays a central role in liver fibrosis. Peroxisome proliferator-activated receptor-¦Ã (PPAR¦Ã) is an important regulator of adipocyte differentiation and has been proposed as a crucial factor for inhibition of HSC activation. The effect of TGF-¦Â1 on PPAR¦Ã in HSCs is largely unknown. This study is aimed to examine whether TGF-¦Â1 can influence PPAR¦Ã expression, focusing on the role of ¦Â-catenin pathway, a key pathway linked to adipogenesis, in TGF-¦Â1 regulation of PPAR¦Ã in cultured HSCs. Our results demonstrated that TGF-¦Â1 evidently inhibited PPAR¦Ã expression and activity in cultured HSCs, which were mediated through ¦Â-catenin pathway. TGF-¦Â1 promoted ¦Â-catenin expression and also increased the stability of ¦Â-catenin protein through ERK1/2/glycogen synthase kinase-3¦Â (GSK-3¦Â) axis in cultured HSCs. Moreover, TGF-¦Â1 inhibition of PPAR¦Ã expression by ¦Â-catenin pathway caused the increase in alpha1(1) collagen and tissue inhibitor of matrix metalloproteinase expression. These results indicated for the first time that TGF-¦Â1 could down-regulate PPAR¦Ã expression through ¦Â-catenin pathway and subsequently contributed to the increase in alpha1(1) collagen level in cultured HSCs.