m6A methyltransferase WTAP regulates myocardial ischemia reperfusion injury through YTHDF1/FOXO3a signaling.
Hui WangLiujing FuYin LiLiudong WeiXiufeng GuHuanming LiJie LiShangyu WenPublished in: Apoptosis : an international journal on programmed cell death (2023)
N 6 -methyladenosine (m 6 A) is emerging as an essential regulator in the progression of myocardial ischemia reperfusion (I/R) injury. However, the in-depth functions and mechanisms for m 6 A are still unclear. This work aimed to explore the potential functions and mechanisms for myocardial I/R injury. In this study, m 6 A methyltransferase WTAP and m 6 A modification level elevated in the hypoxia/reoxygenation (H/R) induced rat cardiomyocytes (H9C2) and I/R injury rat model. Bio-functional cellular experiments demonstrated that knockdown of WTAP remarkably released the proliferation and reduced the apoptosis and inflammatory cytokines induced by H/R. Moreover, exercise training alleviated WTAP level in exercise-trained rats. Mechanistically, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) revealed that a remarkable m 6 A modification site was found in the 3'-UTR of FOXO3a mRNA. Moreover, WTAP triggered the installation of m 6 A modification on FOXO3a mRNA through m 6 A reader YTHDF1, thereby enhancing the stability of FOXO3a mRNA. Collectively, WTAP/YTHDF1/m 6 A/FOXO3a axis regulates the myocardial I/R injury progression, which provides new insights for the treatment of myocardial injury.
Keyphrases
- transcription factor
- signaling pathway
- pi k akt
- left ventricular
- oxidative stress
- ischemia reperfusion injury
- single cell
- cell cycle arrest
- high glucose
- induced apoptosis
- resistance training
- diabetic rats
- high intensity
- rna seq
- physical activity
- binding protein
- cell proliferation
- optical coherence tomography
- dna methylation
- human health