Article Impact Level: HIGH Data Quality: STRONG Summary of Frontiers of Medicine, 18(3), 499–515. https://doi.org/10.1007/s11684-023-1052-4 Dr. Han Wu et al.
Points
- The research investigates the role of the RNA m6A reader YTHDF1 in cardiac fibrosis, particularly following myocardial infarction (MI), using mouse models with manipulated YTHDF1 expression.
- Silencing YTHDF1 improved heart function and reduced myocardial fibrosis, while overexpression worsened cardiac dysfunction and promoted pathological ventricular remodeling.
- YTHDF1 influences the translation of AXL and activates the TGF-β-Smad2/3 signaling pathway, contributing to cardiac dysfunction and fibrosis.
- The study suggests that targeting YTHDF1 could be a promising therapeutic approach for treating cardiac fibrosis and mitigating heart failure post-MI.
- The research provides foundational insights into YTHDF1’s role in fibrosis progression, highlighting its potential for developing personalized cardiac therapies.
Summary
The study delves into the biological functions of the RNA N6-methyladenosine (m6A) reader YTHDF1 in a detailed exploration of cardiac fibrosis, particularly following myocardial infarction (MI). Utilizing adeno-associated virus 9, the researchers manipulated YTHDF1 expression in mouse models, either knocking down or overexpressing the gene. The results significantly underscored the role of YTHDF1 in cardiac health: silencing the gene ameliorated heart function and reduced myocardial fibrosis, whereas overexpression exacerbated cardiac dysfunction and promoted pathological ventricular remodeling.
Further mechanistic insights revealed that the transcriptional activity of the YTHDF1 gene promoter is mediated by the zinc finger BED-type containing 6. This modulation influences the translation of AXL and subsequently activates the transforming growth factor-β (TGF-β)-Smad2/3 signaling pathway, a known contributor to cardiac dysfunction and fibrosis development. These interactions pinpoint the critical pathways YTHDF1 affects heart tissue, suggesting its potential as a therapeutic target in treating cardiac fibrosis.
The study’s findings highlight the potential of targeting YTHDF1 in therapeutic interventions for myocardial fibrosis. The research provides a foundational understanding of its role in fibrosis progression by demonstrating that YTHDF1 facilitates the activation, proliferation, and migration of cardiac fibroblasts. The identification of YTHDF1’s involvement in exacerbating fibrotic conditions offers a promising avenue for developing treatments aimed at mitigating heart failure post-MI, presenting a significant stride toward personalized cardiac therapy.
Link to the article: https://link.springer.com/article/10.1007/s11684-023-1052-4
References Wu, H., Jiang, W., Pang, P., Si, W., Kong, X., Zhang, X., Xiong, Y., Wang, C., Zhang, F., Song, J., Yang, Y., Zeng, L., Liu, K., Jia, Y., Wang, Z., Ju, J., Diao, H., Bian, Y., & Yang, B. (2024). m6A reader YTHDF1 promotes cardiac fibrosis by enhancing AXL translation. Frontiers of Medicine, 18(3), 499–515. https://doi.org/10.1007/s11684-023-1052-4
