Gen-miR-5 derived from Gentianella acuta inhibits PFKP to prevent fibroblast activation and alleviate myocardial fibrosis
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Introduction Myocardial fibrosis (MF) is a key pathological change in heart failure, and lactate a product of glycolysis, is an important component affecting the process of MF. miRNAs derived from Gentianella acuta (G. acuta) have been shown to effectively treat cardiac remodeling. However, whether G. acuta-derived Gen-miR-5 can effectively improve MF remains to be elucidated. This study seeks to explore the pharmacological effects and underlying molecular mechanisms of Gen-miR-5 in the context of Angiotensin II (Ang II) -induced MF. Methods A mouse model of MF was established by subcutaneous infusion of Ang II using osmotic pumps, and then administration of Gen-miR-5 by injection. The effects of Gen-miR-5 in reducing MF and exerting cardioprotective actions were evaluated through pathological morphological analysis and echocardiography. The targeting effect of Gen-miR-5 on PFKP was assessed through dual-luciferase reporter gene assays. Cardiac fibroblasts (CFs) migration abilities were evaluated through wound healing assay and transwell assays. Additionally, the role of Gen-miR-5 in fibroblast activation was investigated using gain- and loss-of-function experiments, and immunofluorescence. Results This study identified six novel specific miRNAs in G. acuta, among which Gen-miR-5 can be absorbed by mice, stably exists in cardiac tissue, and targets the PFKP 3’ UTR to exert cross-kingdom regulatory effects. PFKP, as a key rate-limiting enzyme in the glycolytic pathway, increases lactate accumulation and promotes the proliferation and migration of CFs, thereby facilitating the development of MF. In contrast, Gen-miR-5 alleviates MF by inhibiting this process. Discussion In conclusion, we have elucidated for the first time the pharmacological effects of Gen-miR-5, derived from G. acuta, in inhibiting MF. Gen-miR-5 exerts its cardioprotective effects by targeting and inhibiting the expression of the key glycolytic enzyme PFKP, induced by Ang II, regulating lactate metabolism in fibroblast, and preventing the transformation of fibroblasts into myofibroblasts, ultimately alleviating MF. This study demonstrates that Gen-miR-5 is a potential therapeutic agent for improving cardiac remodeling.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Gen-miR-5 derived from Gentianella acuta inhibits PFKP to prevent fibroblast activation and alleviate myocardial fibrosis
- Date Crossref
- 02/05/2025
- Éditeur
- Frontiers Media SA
- Type
- journal-article
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Où se fait cette recherche
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Shanghai University of Traditional Chinese Medicine Institute of Chinese Materia Medica pays non établi dans la noticeUniversité ou école supérieure
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Hebei University of Chinese Medicine pays non établi dans la noticeUniversité ou école supérieure
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Hebei Science and Technology Department pays non établi dans la noticeOrganisme public
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Hebei Institute of Physical Education pays non établi dans la noticeUniversité ou école supérieure
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Fudan University Department of Cardiology pays non établi dans la noticeUniversité ou école supérieure
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Hebei Key Laboratory of Chinese Medicine Research on Cardio-cerebrovascular Disease pays non établi dans la noticeStructure de recherche
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College of Pharmacy Department of Biochemistry and Molecular Biology pays non établi dans la noticeUniversité ou école supérieure
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Hebei Higher Education Institute Applied Technology Research Center on TCM Development and Industrialization pays non établi dans la noticeStructure de recherche
Institute of Chinese Materia Medica — Shanghai University of Traditional Chinese Medicine, Hebei University of Chinese Medicine et Hebei Science and Technology Department, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.