Potential Relationship Between YTHDF3 and CFTR in Myocardial Ischemia-Reperfusion Injury

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Genetics and Genomics

Background:

• Myocardial ischemia-reperfusion injury (MIRI) worsens outcomes after myocardial infarction and reperfusion therapy.
• Understanding MIRI's regulatory targets is crucial for improving patient prognosis.

Purpose of the Study:

• To identify key regulatory genes and mechanisms involved in myocardial ischemia-reperfusion injury.
• To investigate the roles of YTHDF3 and CFTR in MIRI and their interaction.

Main Methods:

• Analysis of gene expression datasets (GSE123342, GSE6381) to identify differentially expressed genes and hub genes.
• Construction of protein-protein interaction, transcription factor regulatory, and weighted gene co-expression networks.
• In vitro (AC16 cells, OGD/OGR model) and in vivo (rat I/R model) experiments to assess YTHDF3 and CFTR functions.

Main Results:

• CFTR was significantly upregulated in MIRI datasets, while YTHDF3 expression decreased in vitro under injury conditions.
• YTHDF3 overexpression exacerbated MIRI in vitro and in vivo, increasing cell injury and infarct size.
• CFTR overexpression attenuated YTHDF3-induced injury, suggesting a protective role, and CFTR knockdown worsened injury.

Conclusions:

• YTHDF3 is implicated in exacerbating myocardial ischemia-reperfusion injury.
• CFTR plays a protective role against MIRI, potentially counteracting YTHDF3's detrimental effects.
• The YTHDF3-CFTR axis presents a potential therapeutic target for mitigating MIRI.