Tohoku J. Exp. Med., 2013 Jan, 229(1)

Review

Epigenetic Modifications in Hepatic Stellate Cells Contribute to Liver Fibrosis

QI ZHAO,^1,2 CHENG-YONG QIN,² ZE-HUA ZHAO,¹ YU-CHEN FAN^1,3 and KAI WANG^1,3

¹Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shangdong, P.R. China
²Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, Jinan, Shangdong, P.R. China
³Institute of Hepatology, Shandong University, Jinan, Shangdong, P.R. China

Liver fibrosis represents the final common pathway of virtually all types of chronic liver diseases, and it has been a major public health concern. Many genes have been demonstrated to be involved in the pathogenesis of liver fibrosis, while the mechanisms underlying gene regulation still needs further research. On the other hand, hepatic stellate cells (HSCs) are quiescent cells in the perisinusoidal space in liver. HSCs facilitate hepatocytes interactions via releasing soluble inflammatory factors and producing extracellular matrix. HSCs can be activated in response to liver injury, and they differentiate to myofibroblasts, which greatly contribute to the fibrogenesis process. Various epigenetic procedures, including DNA methylation, histone modification and formation of particular chromatin structure, play crucial roles in the gene transcriptional expression in HSCs, regulating various vital processes. For instance, epigenetic modulation on the peroxisome proliferator-activated receptor gamma (PPAR-γ) gene promoter accounts for HSC differentiation through interacting pathways. Aberrant expression of a series of histones and chemokines in activated HSCs can aggravate inflammation and oxidative stress, which in turn promotes differentiation of HSCs to myofibroblasts and enhances the whole fibrogenesis process. Degradation of extracellular matrix is also regulated through epigenetic modulation on matrix associated enzymes. Moreover, fibrosis-related epigenetic modifications in the parental generation may be inherited to their offspring. In this review, we firstly summarize the vital epigenetic modifications of fibrosis-related genes in HSCs, and highlight specific nucleic acid sequences and structures in gene promoters as important action sites, which may provide indicators for liver fibrosis diagnosis in the future.

keywords —— epigenetic modification; gene promoter; hepatic stellate cell; liver fibrosis; methylation

© 2013 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2013, 229, 35-43

Correspondence: Kai Wang, M.D., Ph.D., Department of Hepatology, Qilu Hospital of Shandong University and Institute of Hepatology, Shandong University, 107# Wenhuaxi Road, Jinan, Shangdong 250012, P.R. China.

e-mail: wangdoc876@126.com; wangdoc876@yahoo.com.cn