Related Experiment Video
Updated: Mar 7, 2026
Mouse Electroacupuncture Fixation Device Fabrication for Electroacupuncture Pretreatment in Diabetic Cardiomyopathy Mouse Model
Published on: April 18, 2025
YTHDF2 alleviates diabetic cardiomyopathy by targeting m6A-mediated degradation of lncRNA RMRP and inhibiting
Yanjie Xu1, Wenqi Xiong2, Congcong Xu1
1Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
Abstract:
Diabetic cardiomyopathy (DCM) poses a significant threat to diabetic patients, with NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation playing a critical role. In this research, we identified a previously unrecognized molecular pathway that contributed to DCM pathogenesis, mediated by the long non-coding RNA component of mitochondrial RNA processing endoribonuclease (lncRNA RMRP) and the m6A-recognizing protein YTH domain family protein 2 (YTHDF2). Our data demonstrated a marked elevation in lncRNA RMRP expression in both cardiomyocytes exposed to high glucose (HG) and myocardial tissue from DCM mice. Functionally, lncRNA RMRP aggravated pyroptosis, inflammatory injury, and cardiac dysfunction by stabilizing NLRP3 mRNA and enhancing its expression. Mechanistically, YTHDF2 directly bound to lncRNA RMRP, facilitated its m6A modification and promoted its degradation, thereby negatively regulating NLRP3 expression. Crucially, in vivo rescue experiments confirmed that the cardioprotective effects of YTHDF2 overexpression or lncRNA RMRP knockdown were dependent on the suppression of NLRP3. This study revealed a novel YTHDF2/lncRNA RMRP/NLRP3 regulatory axis in DCM, offering new insights for potential therapeutic interventions.
Insights
Diabetic cardiomyopathy involves NLRP3 inflammasome activation. This study reveals a new pathway involving lncRNA RMRP and YTHDF2 that regulates NLRP3, offering potential therapeutic targets for diabetic heart disease.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- RNA Biology
Background:
- Diabetic cardiomyopathy (DCM) is a major complication of diabetes, significantly increasing morbidity and mortality.
- Activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a key driver of DCM pathogenesis.
- Understanding the molecular regulators of NLRP3 inflammasome in DCM is crucial for developing effective therapies.
Purpose of the Study:
- To elucidate a novel molecular pathway regulating NLRP3 inflammasome activation in diabetic cardiomyopathy.
- To investigate the roles of long non-coding RNA RMRP (lncRNA RMRP) and YTH domain family protein 2 (YTHDF2) in DCM pathogenesis.
- To identify potential therapeutic targets for DCM based on the newly discovered regulatory axis.
Main Methods:
- Assessed lncRNA RMRP expression in high glucose-exposed cardiomyocytes and DCM mouse models.
- Investigated the functional impact of lncRNA RMRP on pyroptosis, inflammation, and cardiac function.
- Examined the interaction between YTHDF2 and lncRNA RMRP, including m6A modification and degradation.
- Performed in vivo rescue experiments to validate the YTHDF2/lncRNA RMRP/NLRP3 axis.
Main Results:
- lncRNA RMRP expression was significantly upregulated in high glucose conditions and DCM myocardial tissue.
- lncRNA RMRP exacerbated DCM by stabilizing NLRP3 mRNA and promoting its expression, leading to pyroptosis and cardiac dysfunction.
- YTHDF2 directly interacted with lncRNA RMRP, promoting its degradation via m6A modification and thereby suppressing NLRP3 expression.
- YTHDF2 overexpression or lncRNA RMRP knockdown demonstrated cardioprotective effects in vivo, contingent on NLRP3 suppression.
Conclusions:
- A novel regulatory axis, YTHDF2/lncRNA RMRP/NLRP3, was identified in the pathogenesis of diabetic cardiomyopathy.
- lncRNA RMRP acts as a crucial mediator in DCM by upregulating NLRP3 inflammasome activation.
- YTHDF2 functions as a negative regulator of this axis, offering a potential therapeutic strategy for DCM.
Related Concept Videos
01:29Cardiomyopathy IV: Restrictive Cardiomyopathy
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy