2026-10-12T23:49:17Z https://www.scidb.cn/oai

10.57760/sciencedb.17238 2025-07-16T16:52:41Z

2025-07-16 YTHDC2 promotes sepsis-induced cardiomyopathy by activating apoptosis and NF-κB pathway doi:10.57760/sciencedb.17238 en Sepsis-induced cardiomyopathy (SICM) is a severe complication of sepsis, especially in children, and identification of novel therapeutic targets remains essential for improving patient outcomes. Recent studies have implicated N6-methyladenosine (m6A), an RNA epigenetic modification, in SICM pathogenesis. However, the role of YTH domain-containing 2 (YTHDC2), an m6A reader protein, in SICM remains unclear. This study used lipopolysaccharide (LPS)-treated adolescent rats, primary cardiomyocytes and H9c2 cardiomyocytes to mimic SICM in vivo and in vitro. We observed a significant upregulation of YTHDC2 in vivo and in vitro. Through comprehensive analyses including RNA-seq, Western blotting, and flow cytometry, we demonstrated that YTHDC2 promotes LPS-induced cardiomyocyte apoptosis. RNA immunoprecipitation sequencing (RIP-seq) and Western blotting further showed that YTHDC2 activates the LPS-induced NF-κB pathway. Mechanistic investigations using RIP-qPCR confirmed direct binding of YTHDC2 to mRNAs encoding the pro-apoptotic proteins BAX and BAK1, as well as the NF-κB subunit p65, with subsequent regulation of NF-κB transcriptional activity. Importantly, adeno-associated virus (AAV9)-mediated cardiac-specific inhibition of YTHDC2 in adolescent rats effectively attenuated LPS-induced cardiomyocyte apoptosis and NF-κB pathway activation. Collectively, our findings establish YTHDC2 as a key regulator in SICM pathogenesis, promoting cardiomyocyte apoptosis and NF-κB signaling activation. These results highlight YTHDC2 as a promising therapeutic target for SICM. m6A; cardiac; sepsis; YTHDC2; apoptosis. Wei Wang Tie-Ning Zhang Zi-Mu Wang Ni Yang Chun-Feng Liu PUBLIC https://creativecommons.org/licenses/by/4.0/ dataset http://www.doi.org/10.1080/21505594.2025.2597565 Science Data Bank