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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

LncRNA MEG3 exacerbates diabetic cardiomyopathy via activating pyroptosis signaling pathway

Provisionally accepted
Shengnan Zhuo Shengnan Zhuo 1,2Yifeng Liu Yifeng Liu 3Siyuan Wang Siyuan Wang 1,2Zhuoling Chen Zhuoling Chen 1,2Xuran Shi Xuran Shi 1,2Yangjunna Zhang Yangjunna Zhang 1,2Dengfeng Xu Dengfeng Xu 4Jingjin Hu Jingjin Hu 1,2Yin Wang Yin Wang 1,2Xuefeng Qu Xuefeng Qu 1,2*
  • 1 School of Pharmacy, Hangzhou Medical College, Hangzhou, China
  • 2 School of Food Science and Engineering, Hangzhou Medical College, Hangzhou, Jiangsu Province, China
  • 3 Bazhong Center for Disease Control and Prevention, Sichuan, China
  • 4 School of Public Health, Hangzhou Medical College, Hangzhou, Jiangsu Province, China

The final, formatted version of the article will be published soon.

    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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