A study in Frontiers of Medicine explores the role of the m 6 A reader YTHDF1 in cardiac fibrosis, a condition characterized by the excessive accumulation of extracellular matrix proteins, leading to the stiffening of the heart and impaired function. Cardiac fibrosis is a common pathological process in various cardiovascular diseases, including hypertension, myocardial infarction , and heart failure. The study focuses on YTHDF1, a protein known to bind to N 6 -methyladenosine (m 6 A), a prevalent internal modification in eukaryotic messenger RNA (mRNA).
m 6 A modification has been implicated in the regulation of a wide range of cellular processes, including mRNA splicing, transport, translation, and degradation. The research reveals that YTHDF1 promotes cardiac fibrosis by enhancing the translation of AXL, a receptor tyrosine kinase known to be involved in tissue repair and fibrosis. Experiments conducted within the study demonstrate that YTHDF1 interacts with AXL mRNA, leading to an increase in AXL protein levels.
This interaction is shown to be crucial for the fibrotic response in cardiac fibroblasts , the cells responsible for producing the extracellular matrix in the heart. The study also finds that the overexpression of YTHDF1 in cardiac fibroblasts results in enhanced cell proliferation and collagen synthesis, hallmarks of fibrosis. Further investigation into the molecular mechanisms at play shows that YTHDF1-mediated AXL translation is regulated by the m 6 A modificati.