外体
再灌注损伤
心肌缺血
缺血
药理学
化学
微泡
医学
生物化学
内科学
小RNA
基因
作者
Tao Yin,N. L. Wang,Fu‐Jun Jia,Yuchao Wu,Lei Gao,Houcheng Zhang,Rongrong Hou
标识
DOI:10.1016/j.ejpb.2024.114218
摘要
Myocardial ischemia/reperfusion (MI/R) injury is the primary cause of postischemic heart failure. The increased expression of Thioredoxin-interacting protein (TXNIP) has been implicated in MI/R injury, although the detailed mechanism remains incompletely understood. In the present study, we observed the up-regulation of the m6A mRNA methylation complex component Wilms' tumor 1-associating protein (WTAP) in MI/R mice, which led to the m6A modification of TXNIP mRNA and an increase in mRNA abundance. Knock-down of WTAP resulted in a significant reduction in the m6A level of TXNIP mRNA and down-regulated TXNIP expression. Moreover, exosomes engineered with ischemic myocardium-targeting peptide (IMTP) were able to deliver WTAP siRNA into ischemic myocardial tissues, resulting in a specific gene knockdown and myocardial protection. In summary, our findings demonstrate that the WTAP-TXNIP regulatory axis plays a significant role in postischemic heart failure, and the use of engineered exosomes targeting the ischemic heart shows promise as a strategy for siRNA therapy to protect the heart from injury.
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