Research Paper Volume 12, Issue 10 pp 9014—9030
miR-125a-5p inhibits glycolysis by targeting hexokinase-II to improve pulmonary arterial hypertension
- 1 Department of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- 2 Department of General Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- 3 Fujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- 4 Fujian Medical University, Fuzhou, China
Received: December 30, 2019 Accepted: March 31, 2020 Published: May 19, 2020https://doi.org/10.18632/aging.103163
How to Cite
Copyright © 2020 Luo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Purpose: The aim of this study was to investigate the effect of microRNAs on the proliferation of pulmonary arterial smooth muscle cells (PASMCs) as a result of targeting hexokinase-II (HK-II) and its mechanism of action.
Results: Differences in metabolic patterns were found between the normal group and monocrotaline-induced pulmonary arterial hypertension (MCT-PH) group. miR-125a-5p decreased glycolysis levels of monocrotaline (MCT)-induced PASMCs by targeting HK-II and inhibiting its proliferation. In vivo experiments found that miR-125a-5p agomir upregulated HK-II expression in the MCT-PH. Right ventricular hypertrophy was reversed and cardiac function improved as a result of decreased mean pulmonary artery pressure (mPAP).
Conclusion: In vitro and in vivo experiments both confirmed that miR-125a-5p could inhibit cell glycolysis and PASMC proliferation to improve PAH by targeting HK-II.
Methods: HK-II overexpression was constructed, and differentially expressed microRNAs were screened for using microarrays. Serum metabolites were detected using Nuclear Magnetic Resonance (NMR). Through screening for characteristic metabolites in rat body fluids and by analyzing biological functions, disordered metabolic pathways were identified. Activity of the miR-125a-5p target HK-II was measured using a luciferase reporter assay. Expression of downstream molecules was measured by RT–qPCR and/or western blot. Glucose consumption and lactic acid production were analyzed and used as a reflection of glycolysis.