The demethylase FTO regulates the m6A modification and inflammation pathway in patients with cardiomyocytes after hypoxia-reoxygenation  

作　　者：ZHAO Hai-mei CHENG Hong JIAO Qi-hui 赵海梅;程红;焦萁荟

机构地区：[1]The Fourth Clinical Medical College,Guangzhou University of Chinese Medicine/Shenzhen Hospital of Traditional Chinese Medicine,Shenzhen 518033,Guangdong,China

出　　处：《South China Journal of Cardiology》2024年第3期169-178,共10页岭南心血管病杂志（英文版）

基　　金：supported by grants from Shenzhen Science and Technology Project(No.JCYJ20220531091817039)。

摘　　要：Background Myocardial ischemia-reperfusion injury is an important clinical problem.Hypoxia-reperfusion(HR)triggers a series of complex cellular reactions and pathological changes.In recent years,the role of N-6-methyladenosine(m6A)modification in gene expression regulation has received extensive attention.New evidence suggests that m6A modifications may play a key role in the regulation of cellular responses to HR-damaged cardiomyocytes.Inflammation is an important part of the pathogenesis of myocardial ischemia-reperfusion injury.In the HR response,inflammatory factors such as interleukin(IL),tumor necrosis factor(TNF-α)and other cytokines are released and activated,which can trigger a series of intracellular signaling pathways leading to myocardial cell damage,apoptosis,and inflammation.In the context of cardiomyocyte H/R injury,it is important to study the relationship between m6A modification and the regulation of inflammatory cytokines expression.It is of great significance to fully understand the underlying mechanism of myocardial ischemia-reperfusion injury and develop new therapeutic strategies.Methods The hypoxic-reoxygenation model of H9C2 cells was established,and the overexpression and knockout model of fat mass and obesity associated gene(FTO)was established.The cells were divided into 6 groups:control group(CG),hypoxic-reperfusion group(HRG),FTO overexpression group(OG),FTO overexpression hypoxic-reperfusion group(OHG),FTO knockout group(KG)and FTO knockout hypoxic-reperfusion group(KHG).The changes of M6A were detected by colorimetry,FTO expression was detected by Western Blot,and the changes of FTO and phosphorylated nuclear factor kappa B(P-NF-κB)were observed by immunofluorescence.IL-6 was detected by enzymelinked immunosorbent assay(ELISA).Results The level of m6A in HRG was significantly higher than that in CG(P<0.05).The same pattern was observed in OG and KG(P<0.05).The level of m6A in KHG were higher than that in HRG,while lower in OHG than that in HRG(P<0.05).The expression of FTO decrea

关 键 词：FTO m6A NF-k B IL-6 Anoxia and reoxygenation 

分 类 号：R542.2[医药卫生—心血管疾病]