YTHDC2 promotes sepsis-induced cardiomyopathy by activating apoptosis and NF-kB pathway
Sepsis-induced cardiomyopathy (SICM) is a severe complication of sepsis, and the identification of novel therapeutic targets remains essential for improving patients outcomes. Recent studies have implicated N6-methyladenosine (m6A), an RNA epigenetic modification, in the pathogenesis of SICM. However, the role of the YTH domain containing 2 (YTHDC2), an m6A reader protein, in SICM remains unknown. This study used lipopolysaccharide (LPS)-treated rats and H9c2 cardiomyocytes to mimic SICM in vivo and in vitro. Then, we observed a significant upregulation of YTHDC2 in vivo and in vitro. RNA-seq identified 2776 differentially expressed genes after YTHDC2 knockdown in LPS-treated H9c2 cardiomyocytes. Moreover, we found that YTHDC2 can regulate the apoptosis of cardiomyocytes through bioinformatic analyses and experimental verification. In addition, the NF-kB pathway was found to be controlled by YTHDC2. Our findings demonstrated that YTHDC2 was upregulated in SICM and contributed to cardiomyocyte apoptosis and NF-kB pathway activation. These results suggest that YTHDC2 may represent a promising therapeutic target for treating SICM, warranting further investigation into its molecular mechanisms and the development of targeted interventions.