Hypoxia induces hypomethylation of the HMGB1 promoter via the MAPK/DNMT1/ HMGB1 pathway in cardiac progenitor cells  

作　　者：Jinwen Su Ming Fang Bei Tian Jun Luo Can Jin Xuejun Wang Zhongping Ning Xinming Li 

机构地区：[1]Department of Cardiology,Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai 201138,China

出　　处：《Acta Biochimica et Biophysica Sinica》2018年第11期1121-1130,共10页生物化学与生物物理学报（英文版）

基　　金：the grants from the Shanghai Pudong New Area Health Planning Commission Industry Special Project (No.PW2013E-2);the Shanghai Municipal Health Planning Commission Key Specialist Project (No.ZK2015A13);the Shanghai Pudong New Area Science Committee Project (No.PKJ2017-Y42);the National Natural Science Foundation of China (No. 81560077).

摘　　要：Apoptosis is involved in the death of cardiac progenitor cells (CPCs)after myocardial infarction (MI) in the heart.The loss of CPCs results in infarct scar and further deterioration of the heart function. Though stem cell-based therapy provides an effective approach for heart function recovery after MI,the retention of CPCs in the infarcted area of the heart is the main barrier that limits its promising therapy.Therefore,the underlying mechanisms of CPC apoptosis in hypoxia are important for the development of new therapeutic targets for MI patients.In this work,we found that the expression of high-mobility group box 1(HMGB1)was upregulated in CPCs under hypoxia conditions. Further study demonstrated that HMGBI was regulated by DNA methyltransferases 1 (DNMT1)via changing the methylation state of CpGs in the promoter of HMGB1 in CPCs duringhypoxia process. Additionally,mitogen-activated protein kinase (MAPK)signaling pathway was found to be involved in regulating DNMT1/HMGB1-mediated CPC apoptosis in hypoxia process.In conclusion,our findings demonstrate a novel regulatory mechanism for CPC apoptosis and proliferation under hypoxia conditions,which may provide a new therapeutic approach for MI patients.

关 键 词：CPCs HYPOXIA HMGB1 DNMT1 MAPKS 

分 类 号：Q[生物学]