Histone demethylase retinoblastoma binding protein 2 regulates the expression of α-smooth muscle actin and vimentin in cirrhotic livers

Abstract

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.

Association between H3K4 methylation and cancer prognosis: A meta‐analysis

“…As transcriptional activators, H3K4me2 and H3K4me3 could promote the expression of downstream genes. Meanwhile, the positive or negative regulatory effects of H3K4me2 and H3K4me3 on carcinogenesis are highly dependent on their interaction with biological and environmental factors . Because the effects of H3K4 methylation may be rather complex, it is important to investigate the influence of different H3K4 methylation patterns on the prognosis of patients with malignant tumors.…”

“…CI, confidence interval; HR, hazard ratio. [17][18][19] Because the effects of H3K4 methylation may be rather complex, it is important to investigate the influence of different H3K4 methylation patterns on the prognosis of patients with malignant tumors. This meta-analysis has several limitations.…”

IOX1 protects from TGF‑β induced fibrosis in LX‑2 cells via the regulation of extracellular matrix protein expression

“…Wang et al (34) reported that expression of histone H3K4 demethylase and retinal-binding protein (RBP2) were increased in the livers of patients with cirrhosis, compared with normal healthy controls. Treatment with RBP2 siRNA in the TGF-β-induced HSC LX-2 cell line increased the H3K4 methylation level and downregulated α-SMA and vimentin, thereby inhibiting the proliferation and activation of HSCs.…”

The Mechanisms of HSC Activation and Epigenetic Regulation of HSCs Phenotypes

“…Retinoblastoma binding protein 2 (RBP2) is also an H3K4 demethylase and has been found in cirrhotic rat livers where its expression is stimulated by TGFβ. Depletion of RBP2 leads to reduced HSC proliferation and decreased levels of α-SMA and vimentin, suggesting that RBP2 may be a potential target in treatment of liver fibrosis [69]. …”