Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis

Shi-Yi Lyu; Wang Xiao; Guang-Zu Cui; Cheng Yu; Huan Liu; Min Lyu; Qian-Ya Kuang; En-Hua Xiao; Yong-Heng Luo

doi:10.3389/fgene.2023.1124330

Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis

Front Genet. 2023 Mar 28:14:1124330. doi: 10.3389/fgene.2023.1124330. eCollection 2023.

Authors

Shi-Yi Lyu¹, Wang Xiao², Guang-Zu Cui³, Cheng Yu¹, Huan Liu¹, Min Lyu¹, Qian-Ya Kuang¹, En-Hua Xiao¹, Yong-Heng Luo¹

Affiliations

¹ Department of Radiology, The Second Xiangya Hospital, Central-South University, Changsha, Hunan, China.
² Department of Gastrointestinal Surgery, The Second Xiangya Hospital, Central-South University, Changsha, Hunan, China.
³ XiangYa School of Medicine, Central South University, Changsha, Hunan, China.

Abstract

Liver fibrosis is a repair response to injury caused by various chronic stimuli that continually act on the liver. Among them, the activation of hepatic stellate cells (HSCs) and their transformation into a myofibroblast phenotype is a key event leading to liver fibrosis, however the mechanism has not yet been elucidated. The molecular basis of HSC activation involves changes in the regulation of gene expression without changes in the genome sequence, namely, via epigenetic regulation. DNA methylation is a key focus of epigenetic research, as it affects the expression of fibrosis-related, metabolism-related, and tumor suppressor genes. Increasing studies have shown that DNA methylation is closely related to several physiological and pathological processes including HSC activation and liver fibrosis. This review aimed to discuss the mechanism of DNA methylation in the pathogenesis of liver fibrosis, explore DNA methylation inhibitors as potential therapies for liver fibrosis, and provide new insights on the prevention and clinical treatment of liver fibrosis.

Keywords: DNA methylation; DNA methylation inhibitors; epigenetics; hepatic fibrosis; hepatic stellate cells (HSCs).

Publication types

Review

Grants and funding

This study was supported by the Natural Science Foundation of Hunan Province No.2021JJ30945 (to Y-HL), Center for Medical Imaging in Hunan Province (2020SK4001) and the Fundamental Research Funds for the Central Universities of Central South University (2023ZZTS0880).