Work

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

Year: 2026

Type: article

Abstract: 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. • SIK1 reverses H/R-induced apoptosis and ROS levels. • SIK1 reverses the effects of H/R on Cytochrome C, Caspase-9/12, MEF2 and SIRT1. • MEF2 silencing reverses the regulation of cells by SIK1 overexpression. • SIK1 enhances MEF2-mediated SIRT1 activation, reducing myocardial damage.

Source: Molecular and Cellular Probes

DOI: 10.1016/j.mcp.2026.102065

Authors: Linhui Gong, Ling Chen, Suxia Han, Lezhi Sheng

Institution: Pudong New Area People's Hospital

Language: English

Topic: Cardiac Ischemia and Reperfusion

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,790