Gen-miR-5 derived from Gentianella acuta inhibits PFKP to prevent fibroblast activation and alleviate myocardial fibrosis
IntroductionMyocardial 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...
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Frontiers Media S.A.
2025-05-01
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| author | Hongyao Ge Zhenyu Du Weizhe Liu Weizhe Liu Weizhe Liu Letian Wang Junyang Li Gaoshan Yang Gaoshan Yang Gaoshan Yang Aiying Li Aiying Li Aiying Li |
| author_facet | Hongyao Ge Zhenyu Du Weizhe Liu Weizhe Liu Weizhe Liu Letian Wang Junyang Li Gaoshan Yang Gaoshan Yang Gaoshan Yang Aiying Li Aiying Li Aiying Li |
| author_sort | Hongyao Ge |
| collection | DOAJ |
| description | IntroductionMyocardial 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.MethodsA 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.ResultsThis 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.DiscussionIn 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. |
| format | Article |
| id | doaj-art-310f515a02ad4e509a7b5ace19f089c9 |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-310f515a02ad4e509a7b5ace19f089c92025-08-20T02:56:35ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15788771578877Gen-miR-5 derived from Gentianella acuta inhibits PFKP to prevent fibroblast activation and alleviate myocardial fibrosisHongyao Ge0Zhenyu Du1Weizhe Liu2Weizhe Liu3Weizhe Liu4Letian Wang5Junyang Li6Gaoshan Yang7Gaoshan Yang8Gaoshan Yang9Aiying Li10Aiying Li11Aiying Li12Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaHebei Key Laboratory of Chinese Medicine Research on Cardio-cerebrovascular Disease, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Chinese Medicine Research on Cardio-cerebrovascular Disease, Shijiazhuang, Hebei, ChinaHebei Higher Education Institute Applied Technology Research Center on TCM Development and Industrialization, Shijiazhuang, Hebei, ChinaDepartment of Biochemistry and Molecular Biology, College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, ChinaDepartment of Cardiology, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, ChinaDepartment of Biochemistry and Molecular Biology, College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Chinese Medicine Research on Cardio-cerebrovascular Disease, Shijiazhuang, Hebei, ChinaHebei Higher Education Institute Applied Technology Research Center on TCM Development and Industrialization, Shijiazhuang, Hebei, ChinaDepartment of Biochemistry and Molecular Biology, College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Chinese Medicine Research on Cardio-cerebrovascular Disease, Shijiazhuang, Hebei, ChinaHebei Higher Education Institute Applied Technology Research Center on TCM Development and Industrialization, Shijiazhuang, Hebei, ChinaDepartment of Biochemistry and Molecular Biology, College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, ChinaIntroductionMyocardial 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.MethodsA 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.ResultsThis 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.DiscussionIn 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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1578877/fullplant-derived miRNAsPFKPlactatefibroblast activationmyocardial fibrosis |
| spellingShingle | Hongyao Ge Zhenyu Du Weizhe Liu Weizhe Liu Weizhe Liu Letian Wang Junyang Li Gaoshan Yang Gaoshan Yang Gaoshan Yang Aiying Li Aiying Li Aiying Li Gen-miR-5 derived from Gentianella acuta inhibits PFKP to prevent fibroblast activation and alleviate myocardial fibrosis Frontiers in Pharmacology plant-derived miRNAs PFKP lactate fibroblast activation myocardial fibrosis |
| title | Gen-miR-5 derived from Gentianella acuta inhibits PFKP to prevent fibroblast activation and alleviate myocardial fibrosis |
| title_full | Gen-miR-5 derived from Gentianella acuta inhibits PFKP to prevent fibroblast activation and alleviate myocardial fibrosis |
| title_fullStr | Gen-miR-5 derived from Gentianella acuta inhibits PFKP to prevent fibroblast activation and alleviate myocardial fibrosis |
| title_full_unstemmed | Gen-miR-5 derived from Gentianella acuta inhibits PFKP to prevent fibroblast activation and alleviate myocardial fibrosis |
| title_short | Gen-miR-5 derived from Gentianella acuta inhibits PFKP to prevent fibroblast activation and alleviate myocardial fibrosis |
| title_sort | gen mir 5 derived from gentianella acuta inhibits pfkp to prevent fibroblast activation and alleviate myocardial fibrosis |
| topic | plant-derived miRNAs PFKP lactate fibroblast activation myocardial fibrosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1578877/full |
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