Myocardial injury is a severe complication of sepsis and contributes substantially to the death of critically ill patients. Long non-coding RNAs (lncRNAs) participate in the pathogenesis of sepsis-induced myocardial injury. In this study, we investigated the role of lncRNA X-inactive specific transcript (XIST) in septic myocardial injury and explored its mechanism. Lipopolysaccharide (LPS)-stimulated H9C2 cells and rats subjected to cecal ligation and puncture (CLP) were used as the in vitro and in vivo models. After exposure to LPS, XIST and c-Fos levels were upregulated, but miR-150-5p was downregulated in H9C2 cardiomyocytes and myocardial tissues. XIST affected viability, apoptosis, and pyroptosis in LPS-challenged H9C2 cells. Moreover, XIST knockdown attenuated LPS-induced injury in H9C2 cells by targeting the miR-150-5p/c-Fos axis. c-Fos could bound to the promoter of the TXNIP/XIST gene and enhanced TXNIP/XIST expression. Silencing of XIST improved cardiac function and survival rate and reduced apoptosis and pyroptosis by regulating the miR-150-5p/c-Fos axis in septic rats in vivo. Taken together, our data show that XIST/miR-150-5p/c-Fos axis affected septic myocardial injury, which may indicate a novel therapeutic strategy for sepsis-induced myocardial injury.
Find this article in full text from Springer Verlag.