组蛋白去甲基化酶视网膜母细胞瘤结合蛋白2调节肝硬化肝脏中α-平滑肌肌动蛋白和波形蛋白的表达。
Histone demethylase retinoblastoma binding protein 2 regulates the expression of α-smooth muscle actin and vimentin in cirrhotic livers.
作者信息
Wang Q, Wang L X, Zeng J P, Liu X J, Liang X M, Zhou Y B
机构信息
Shandong University, Department of Microbiology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Medicine, Jinan, China.
出版信息
Braz J Med Biol Res. 2013 Sep;46(9):739-45. doi: 10.1590/1414-431X20132843. Epub 2013 Sep 6.
Liver cirrhosis is one of the most common diseases of Chinese patients. Herein, we report the high expression of a newly identified histone 3 lysine 4 demethylase, retinoblastoma binding protein 2 (RBP2), and its role in liver cirrhosis in humans. The siRNA knockdown of RBP2 expression in hepatic stellate cells (HSCs) reduced levels of α-smooth muscle actin (α-SMA) and vimentin and decreased the proliferation of HSCs; and overexpression of RBP2 increased α-SMA and vimentin levels. Treatment with transforming growth factor β (TGF-β) upregulated the expression of RBP2, α-SMA, and vimentin, and the siRNA knockdown of RBP2 expression attenuated TGF-β-mediated upregulation of α-SMA and vimentin expression and HSC proliferation. Furthermore, RBP2 was highly expressed in cirrhotic rat livers. Therefore, RBP2 may participate in the pathogenesis of liver cirrhosis by regulating the expression of α-SMA and vimentin. RBP2 may be a useful marker for the diagnosis and treatment of liver cirrhosis.
肝硬化是中国患者最常见的疾病之一。在此，我们报告一种新鉴定的组蛋白3赖氨酸4去甲基化酶——视网膜母细胞瘤结合蛋白2（RBP2）的高表达及其在人类肝硬化中的作用。肝星状细胞（HSC）中RBP2表达的小干扰RNA（siRNA）敲低降低了α平滑肌肌动蛋白（α-SMA）和波形蛋白的水平，并减少了HSC的增殖；而RBP2的过表达增加了α-SMA和波形蛋白的水平。转化生长因子β（TGF-β）处理上调了RBP2、α-SMA和波形蛋白的表达，RBP2表达的siRNA敲低减弱了TGF-β介导的α-SMA和波形蛋白表达上调以及HSC增殖。此外，RBP2在肝硬化大鼠肝脏中高表达。因此，RBP2可能通过调节α-SMA和波形蛋白的表达参与肝硬化的发病机制。RBP2可能是肝硬化诊断和治疗的有用标志物。
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