miR-124-3p downregulates EGR1 to suppress ischemia-hypoxia reperfusion injury in human iPS cell-derived cardiomyocytes

• Published in: Scientific reports Vol. 14; no. 1; pp. 14811 - 11
• Main Authors: Yang, Qiaoke, Murata, Kozue, Ikeda, Tadashi, Minatoya, Kenji, Masumoto, Hidetoshi
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 27.06.2024; Nature Publishing Group UK; Nature Portfolio
• Subjects: Apoptosis; Cardiomyocytes; Cardiovascular diseases; Caspase-3; Cell death; Congestive heart failure; Down-Regulation; Early Growth Response Protein 1 - genetics; Early Growth Response Protein 1 - metabolism; EGR-1 protein; Heart diseases; Humans; Hypoxia; Immunofluorescence; Induced Pluripotent Stem Cells - metabolism; Ischemia; MicroRNAs - genetics; MicroRNAs - metabolism; mRNA; Myocardial Reperfusion Injury - genetics; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocytes, Cardiac - metabolism; Pluripotency; Polymerase chain reaction; Reperfusion; siRNA; Stem cells; Western blotting
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-65373-x

Ischemic heart diseases are a major global cause of death, and despite timely revascularization, heart failure due to ischemia-hypoxia reperfusion (IH/R) injury remains a concern. The study focused on the role of Early Growth Response 1 (EGR1) in IH/R-induced apoptosis in human cardiomyocytes (CMs). Human induced pluripotent stem cell (hiPSC)-derived CMs were cultured under IH/R conditions, revealing higher EGR1 expression in the IH/R group through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). Immunofluorescence analysis (IFA) showed an increased ratio of cleaved Caspase-3-positive apoptotic cells in the IH/R group. Using siRNA for EGR1 successfully downregulated EGR1, suppressing cleaved Caspase-3-positive apoptotic cell ratio. Bioinformatic analysis indicated that EGR1 is a plausible target of miR-124-3p under IH/R conditions. The miR-124-3p mimic, predicted to antagonize EGR1 mRNA, downregulated EGR1 under IH/R conditions in qRT-PCR and WB, as confirmed by IFA. The suppression of EGR1 by the miR-124-3p mimic subsequently reduced CM apoptosis. The study suggests that treatment with miR-124-3p targeting EGR1 could be a potential novel therapeutic approach for cardioprotection in ischemic heart diseases in the future.