SIK1 alleviates myocardial hypoxia-reperfusion injury via promoting MEF2-mediated SIRT1 transcription

Myocardial Hypoxia-Reperfusion (H/R) injury is a major challenge in coronary artery disease treatment. This article explores the potential mechanism of salt inducible kinase 1 (SIK1) in H/R injury. This study used H9C2 cardiomyocytes as the model. By constructing SIK1 overexpression and myocyte enhancer factor 2 (MEF2) silencing vectors, and combining qRT-PCR, CCK8, 5-Ethynyl-2′-deoxyuridine, flow cytometry, Western blot, JASPAR prediction, luciferase assay and chromatin immunoprecipitation experiments, it explored the effects and mechanisms of SIK1 on H/R cardiomyocytes from multiple dimensions. H/R impaired H9C2 cells (reduced viability, increased apoptosis/ROS/Caspase-9/12/Cytochrome C, downregulated MEF2/Sirtuin 1 (SIRT1)), which SIK1 overexpression reversed. MEF2 silencing blocked SIK1's protection; JASPAR, luciferase assay and Chromatin Immunoprecipitation confirmed MEF2 directly bound to SIRT1 promoter and activated its transcription. SIK1 alleviates H/R-induced myocardial cell damage in association with the upregulation of MEF2 and subsequent MEF2-mediated transcriptional activation of SIRT1.