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

被引：15

作者：

Lyu, Shi-Yi ^{[1
]}

Xiao, Wang ^{[2
]}

Cui, Guang-Zu ^{[3
]}

Yu, Cheng ^{[1
]}

Liu, Huan ^{[1
]}

Lyu, Min ^{[1
]}

Kuang, Qian-Ya ^{[1
]}

Xiao, En-Hua ^{[1
]}

Luo, Yong-Heng ^{[1
]}

机构：

[1] Cent South Univ, Xiangya Hosp 2, Dept Radiol, Changsha, Hunan, Peoples R China

[2] Cent South Univ, Xiangya Hosp 2, Dept Gastrointestinal Surg, Changsha, Hunan, Peoples R China

[3] Cent South Univ, XiangYa Sch Med, Changsha, Hunan, Peoples R China

来源：

FRONTIERS IN GENETICS | 2023年 / 14卷

关键词：

hepatic fibrosis; DNA methylation; epigenetics; hepatic stellate cells (HSCs); DNA methylation inhibitors; LIVER FIBROSIS; STELLATE CELLS; MYOFIBROBLAST TRANSDIFFERENTIATION; TUMOR-SUPPRESSOR; MECP2; CONTROLS; CANCER-CELLS; MDX MICE; ACTIVATION; EXPRESSION; ZEBULARINE;

D O I：

10.3389/fgene.2023.1124330

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：11

共 116 条

[1] Hepatocyte mitochondria-derived danger signals directly activate hepatic stellate cells and drive progression of liver fibrosis [J].

An, Ping ;

Wei, Lin-Lin ;

Zhao, Shuangshuang ;

Sverdlov, Deanna Y. ;

Vaid, Kahini A. ;

Miyamoto, Makoto ;

Kuramitsu, Kaori ;

Lai, Michelle ;

Popov, Yury, V .

NATURE COMMUNICATIONS, 2020, 11 (01)

[2] Methylation determines fibroblast activation and fibrogenesis in the kidney [J].

Bechtel, Wibke ;

McGoohan, Scott ;

Zeisberg, Elisabeth M. ;

Mueller, Gerhard A. ;

Kalbacher, Hubert ;

Salant, David J. ;

Mueller, Claudia A. ;

Kalluri, Raghu ;

Zeisberg, Michael .

NATURE MEDICINE, 2010, 16 (05) :544-U75

[3] Metabolic activation of zebularine, a novel DNA methylation inhibitor, in human bladder carcinoma cells [J].

Ben-Kasus, T ;

Ben-Zvi, Z ;

Marquez, VE ;

Kelley, JA ;

Agbaria, R .

BIOCHEMICAL PHARMACOLOGY, 2005, 70 (01) :121-133

[4] Repression of Smad7 mediated by DNMT1 determines hepatic stellate cell activation and liver fibrosis in rats [J].

Bian, Er-Bao ;

Huang, Cheng ;

Wang, Hua ;

Chen, Xiao-Xia ;

Zhang, Lei ;

Lv, Xiong-Wen ;

Li, Jun .

TOXICOLOGY LETTERS, 2014, 224 (02) :175-185

[5] Shikonin derivatives for cancer prevention and therapy [J].

Boulos, Joelle C. ;

Rahama, Muhammad ;

Hegazy, Mohamed-Elamir F. ;

Efferth, Thomas .

CANCER LETTERS, 2019, 459 :248-267

[6] Epigenome-Wide Analysis of Methylation Changes in the Sequence of Gallstone Disease, Dysplasia, and Gallbladder Cancer [J].

Braegelmann, Johannes ;

Barahona Ponce, Carol ;

Marcelain, Katherine ;

Roessler, Stephanie ;

Goeppert, Benjamin ;

Gallegos, Ivan ;

Colombo, Alicia ;

Sanhueza, Veronica ;

Morales, Erik ;

Rivera, Maria Teresa ;

de Toro, Gonzalo ;

Ortega, Alejandro ;

Muller, Bettina ;

Gabler, Fernando ;

Scherer, Dominique ;

Waldenberger, Melanie ;

Reischl, Eva ;

Boekstegers, Felix ;

Garate-Calderon, Valentina ;

Umu, Sinan U. ;

Rounge, Trine B. ;

Popanda, Odilia ;

Lorenzo Bermejo, Justo .

HEPATOLOGY, 2021, 73 (06) :2293-2310

[7] Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases [J].

Brueckner, B ;

Boy, RG ;

Siedlecki, P ;

Musch, T ;

Kliem, HC ;

Zielenkiewicz, P ;

Suhai, S ;

Wiessler, M ;

Lyko, F .

CANCER RESEARCH, 2005, 65 (14) :6305-6311

[8] Endurance capacity in maturing mdx mice is markedly enhanced by combined voluntary wheel running and green tea extract [J].

Call, Jarrod A. ;

Voelker, Kevin A. ;

Wolff, Andrew V. ;

McMillan, Ryan P. ;

Evans, Nick P. ;

Hulver, Matthew W. ;

Talmadge, Robert J. ;

Grange, Robert W. .

JOURNAL OF APPLIED PHYSIOLOGY, 2008, 105 (03) :923-932

[9] Activation of SIRT6 by DNA hypomethylating agents and clinical consequences on combination therapy in leukemia [J].

Carraway, Hetty E. ;

Malkaram, Sridhar A. ;

Cen, Yana ;

Shatnawi, Aymen ;

Fan, Jun ;

Ali, Hamdy E. A. ;

Abd Elmageed, Zakaria Y. ;

Buttolph, Thomm ;

Denvir, James ;

Primerano, Donald A. ;

Fandy, Tamer E. .

SCIENTIFIC REPORTS, 2020, 10 (01)

[10] Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer [J].

Cebola, Ines ;

Custodio, Joaquin ;

Munoz, Mar ;

Diez-Villanueva, Anna ;

Pare, Laia ;

Prieto, Patricia ;

Ausso, Susanna ;

Coll-Mulet, Llorenc ;

Bosca, Lisardo ;

Moreno, Victor ;

Peinado, Miguel A. .

CLINICAL EPIGENETICS, 2015, 7

← 1 2 3 4 5 6 7 8 9 10 →