miR‑320a in serum exosomes promotes myocardial fibroblast proliferation via regulating the PIK3CA/Akt/mTOR signaling pathway in HEH2 cells

Wang,Qing-Gao; Cheng,Brian Chi‑Yan; He,Ya-Zhou; Li,Li-Juan; Ling,Yun; Luo,Gan; Wang,Li; Liang,Shan; Zhang,Yi

doi:10.3892/etm.2021.10305

miR‑320a in serum exosomes promotes myocardial fibroblast proliferation via regulating the PIK3CA/Akt/mTOR signaling pathway in HEH2 cells

Authors:
- Qing-Gao Wang
- Brian Chi‑Yan Cheng
- Ya-Zhou He
- Li-Juan Li
- Yun Ling
- Gan Luo
- Li Wang
- Shan Liang
- Yi Zhang
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Affiliations: Department of Cardiology, First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region 530023, P.R. China, College of Professional and Continuing Education, The Hong Kong Polytechnic University, Hong Kong 999077, SAR, P.R. China, School of Nursing, Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region 530200, P.R. China, Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, P.R. China
Published online on: June 14, 2021 https://doi.org/10.3892/etm.2021.10305
Article Number: 873
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRNAs/miRs) serve an important role in the pathogenesis of chronic heart failure (CHF). A number of reports have illustrated the regulatory effect of serum exosomal miRNA on myocardial fibrosis. The present study aimed to investigate the expression of miR‑320a in serum exosomes, as well as the effect of miR‑320a on myocardial fibroblast proliferation. Serum exosome samples from 10 patients with CHF and 5 healthy volunteers were obtained and characterized. mRNA and protein expression levels were measured via reverse transcription‑quantitative PCR and western blotting, respectively. The content of soluble growth stimulation expressed gene 2 (sST2) was determined via ELISA. HEH2 cell viability and apoptosis were detected by performing MTT assays and flow cytometry, respectively. The results demonstrated that serum miR‑320a expression levels and sST2 content were significantly increased in patients with CHF compared with healthy controls, and the expression of serum miR‑320a was significantly correlated with clinical CHF indexes. miR‑320a expression levels were significantly increased in exosomes isolated from patients with CHF compared with those isolated from healthy controls. Phosphoinositide‑3‑kinase catalytic α polypeptide gene (PIK3CA) expression levels and sST2 content were increased in HEH2 cells following transfection with miR‑320a mimics compared with NC‑mimic, whereas miR‑320a inhibitor displayed contrasting effects by reduced the cell viability and apoptosis in myocardial fibroblasts compared with the NC‑inhibitor group. The protein expression levels of collagen I, collagen III, α‑smooth muscle actin, phosphorylated (p)‑mTOR (ser 2448)/mTOR, p‑Akt (ser 473)/Akt, p‑Akt (thr 308)/Akt and PIK3CA were significantly increased in miR‑320a mimic‑transfected HEH2 cells compared with the NC‑mimics groups. By contrast, miR‑320a inhibitor notably downregulated the expression levels of these proteins compared with the NC‑inhibitor group. Collectively, the results of the present study demonstrated that miR‑320a promoted myocardial fibroblast proliferation via regulating the PIK3CA/Akt/mTOR signaling pathway in HEH2 cells, suggesting that serum exosomal miR‑320a may serve as a potential biomarker for the diagnosis of CHF.

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