5-Azacytidine modulates interferon regulatory factor 1 in macrophages toexert a cardioprotective effect

Collection with item attached
2015
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473447.do
DOI
10.1038/srep15768
Title
5-Azacytidine modulates interferon regulatory factor 1 in macrophages toexert a cardioprotective effect
Description
This study was supported by a grant of the National Research Foundationof Korea Grant funded by the Korean Government (MEST), Republic of Korea(2010-0020261, 2011-0024852), and the Korean Health Technology R&DProject, Ministry of Health & Welfare, Republic of Korea (HI12C0199,HI13C1527).
abstract
Macrophages are actively involved in inflammatory responses during the progression of cardiac injury, including myocardial infarction (MI). A previous study showed that 5-azacytidine (5AZ), a DNA methylation inhibitor, can ameliorate cardiac injury by shifting macrophages toward an anti-inflammatory phenotype via iNOS inhibition. Here, we show that the beneficial effect of 5AZ is associated with sumoylation of interferon regulatory factor-1 (IRF1) in macrophages. IRF1 is a critical transcription factor for iNOS induction and is antagonized by IRF2. In the stimulated macrophages, IRF1 accumulated in the nucleus without degradation by 5AZ treatment. In animal study, 5AZ administration resulted in significant improvements in cardiac function and fibrosis. IRF1-expressing macrophages were more abundant in the 5AZ-treated MI group than in the PBS-treated MI group. Because sumoylated IRF1 is known to mimic IRF2, we examined the IRF1 sumoylation. Sumoylated IRF1 was resistant to degradation and significantly increased in the 5AZ-treated MI group. Collectively, 5AZ had a protective effect after MI by potentiation of IRF1 sumoylation and is suggested as a novel therapeutic intervention for cardiac repair.
provenance
Made available in Cube on 2018-09-28T10:19:49Z (GMT). No. of bitstreams: 0
language
English
author
Jeong, Hye-yun
Kang, Wan Seok
Hong, Moon Hwa
Jeong, Hae Chang
Shin, Myun-Geun
Jeong, Myung Ho
Kim, Yong Sook
Ahn, Youngkeun
accessioned
2018-09-28T10:19:49Z
available
2018-09-28T10:19:49Z
issued
2015
citation
SCIENTIFIC REPORTS(5)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473447.do
Funder
교육부
Funding Program
이공학개인기초연구지원
Project ID
1345235183
Jurisdiction
Rep.of Korea
Project Name
Development of technique in optimized stem cell therapy and evaluation of safety to porcine myocardial infarction model
rights
openAccess
type
article


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