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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1538059
This article is part of the Research Topic Innovative Approaches and Molecular Mechanisms in Cardiovascular Pharmacology View all 8 articles
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Diabetic cardiomyopathy (DCM) is a prevalent complication observed in diabetic patients. The long non-coding RNA maternally expressed gene 3 (lncMEG3) has been found to be intricately associated with myocardial infarction and heart failure. However, the role of lncMEG3 in DCM remains unclear. The present study was designed to investigate the role of lncMEG3 in DCM and elucidate the underlying molecular mechanisms. The diabetic mouse model was established through intraperitoneal injection streptozotocin (STZ). The heart-targeted adeno-associated virus carrying lncMEG3 interfering RNA (AAV9-shMEG3) was administered via tailvein injection to induce silencing of lncMEG3 in diabetic mice. Echocardiography was performed to evaluate cardiac function, while hematoxylin and eosin (H&E) staining and Masson trichrome staining were employed for the detection of cardiac remodeling. The underlying mechanisms were investigated using western blot and real-time PCR (qPCR). The expression of lncMEG3 was increased in hearts with DCM and in AC16 cardiomyocytes treated with high glucose. The knockout of lncMEG3 reduced inflammation, cardiac fibrosis and myocardial hypertrophy, and improved cardiac dysfunction in diabetic mice. In diabetic mice, the activation of the nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3)-inflammasome was observed, whereas silencing of lncMEG3 resulted in a reduction in NLRP3 inflammasome activation. Mechanistically, we discovered that lncMEG3 specifically functions as a competitive inhibitor of miR-223. Moreover, the use of miR-223 antisense oligonucleotide (AMO) counteracted the suppressive effects of lncMEG3 knockdown on NLRP3 inflammasome activation induced by high glucose in vitro. In summary, lncMEG3 exacerbates DCM by enhancing NLRP3 inflammasome activation through attenuating miR-223-mediated degradation of NLRP3 in the hearts of individuals with diabetes.
Keywords: Diabetic cardiomyopathy, LncMEG3, miR-223, pyroptosis, Cardiac function.
Received: 02 Dec 2024; Accepted: 21 Mar 2025.
Copyright: © 2025 Zhuo, Liu, Wang, Chen, Shi, Zhang, Xu, Hu, Wang and Qu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xuefeng Qu, School of Pharmacy, Hangzhou Medical College, Hangzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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