Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Oct 8, 2016; 8(28): 1194-1199
Published online Oct 8, 2016. doi: 10.4254/wjh.v8.i28.1194
DNA methylation of angiotensin II receptor gene in nonalcoholic steatohepatitis-related liver fibrosis
Kiyoshi Asada, Yosuke Aihara, Hiroaki Takaya, Ryuichi Noguchi, Tadashi Namisaki, Kei Moriya, Masakazu Uejima, Mitsuteru Kitade, Tsuyoshi Mashitani, Kosuke Takeda, Hideto Kawaratani, Yasushi Okura, Kosuke Kaji, Akitoshi Douhara, Yasuhiko Sawada, Norihisa Nishimura, Kenichiro Seki, Akira Mitoro, Junichi Yamao, Hitoshi Yoshiji
Kiyoshi Asada, Yosuke Aihara, Hiroaki Takaya, Ryuichi Noguchi, Tadashi Namisaki, Kei Moriya, Masakazu Uejima, Mitsuteru Kitade, Tsuyoshi Mashitani, Kosuke Takeda, Hideto Kawaratani, Yasushi Okura, Kosuke Kaji, Akitoshi Douhara, Yasuhiko Sawada, Norihisa Nishimura, Kenichiro Seki, Akira Mitoro, Junichi Yamao, Hitoshi Yoshiji, Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan
Author contributions: Asada K performed the majority of experiments and analyzed the data; Aihara Y and Takaya H performed the molecular investigations; Noguchi R, Namisaki T, Moriya K, Uejima M, Kitade M, Mashitani T, Takeda K, Kawaratani H, Okura Y, Kaji K, Douhara A, Sawada Y, Nishimura N and Seki K participated in treatment of animals; Mitoro A, Yamao J and Yoshiji H designed and coordinated the research; Asada K, Kaji K and Yoshiji H wrote the paper.
Institutional review board statement: As for the file of Institutional review board statement, it is not applicable to my study because no human subjects were analyzed in my study.
Institutional animal care and use committee statement: This study was approved by the animal experimental ethical committee at the Nara Medical University (No. 9354).
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kiyoshi Asada, MD, PhD, Research Scientist, Third Department of Internal Medicine, Nara Medical University, 840 Shijocho, Kashihara, Nara 634-8521, Japan. kasada@naramed-u.ac.jp
Telephone: +81-744-223051 Fax: +81-744-247122
Received: May 20, 2016
Peer-review started: May 21, 2016
First decision: July 4, 2016
Revised: July 8, 2016
Accepted: August 27, 2016
Article in press: August 29, 2016
Published online: October 8, 2016
Core Tip

Core tip: We report the first study to show that Agtr1a methylation occurred during the development of nonalcoholic steatohepatitis-related liver fibrosis. Interestingly, Agtr1a gene expression was upregulated during liver fibrosis, although Agtr1a was methylated. This study demonstrates for the first time that renin-angiotensin system-related gene expression is regulated by DNA methylation during liver fibrosis. This finding raises expectations about the therapeutic application of demethylating agents for the treatment of liver fibrosis.