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MicroRNA-9 regulates cardiac fibrosis by targeting PDGFR-β in rats

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Abstract

The proliferation of cardiac fibroblasts (CFs) and excessive deposition of extracellular matrix (ECM) are the main pathological characteristics of cardiac fibrosis. In recent years, microRNAs (miRNAs) have been found to be a new kind of regulator in cardiac fibrosis. The purpose of this study was to investigate the role of microRNA-9 (miR-9) in the process of cardiac fibrosis and its mechanism. Treatment of cultured neonatal rat CFs with PDGF-BB or serum suppressed the expression of miR-9. Overexpression of miR-9 obviously inhibited neonatal rat CFs proliferation and collagen production as detected by MTT assays, qRT-PCR, and western blotting. The effects of miR-9 in CFs were abrogated by co-transfection with miR-9 inhibitors. Overexpression of miR-9 reduced the mRNA and protein levels of PDGFR-βand its downstream protein, extracellular signal-regulated kinase (ERK) 1/2. Silencing PDGFR-βby small interfering RNA mimicked the anti-fibrotic action of miR-9, whereas overexpression of PGDFR-β canceled the effect of miR-9 in cultured CFs. Dual-luciferase reporter assays showed that PDGFR-βwas a direct target of miR-9. Overexpression of miR-9 inhibited cardiac fibrosis by targeting PDGFR-β, indicating that miR-9 might play a role in the treatment of cardiac fibrosis.

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Abbreviations

PDGF:

Platelet-derived growth factor

PDGFR:

Platelet-derived growth factor receptor

miRNA:

microRNA

miR-9:

microRNA-9

CFs:

Cardiac fibroblasts

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

ECM:

Extracellular matrix

ERK:

Extracellular signal regulated kinase

UTR:

Untranslated region

siRNA:

Small interfering RNA

DMSO:

Dimethyl sulphoxide

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Authors and Affiliations

  1. Department of Cardiology, Anhui Provincial Hospital Affiliated to Anhui Medical University, No. 17 Lujiang Road, Hefei, 230001, China

    Lei Wang, LiKun Ma, Hai Fan, Zhe Yang, LongWei Li & HanZhang Wang

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  1. Lei Wang
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  2. LiKun Ma
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  3. Hai Fan
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  4. Zhe Yang
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  5. LongWei Li
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Correspondence to LiKun Ma.

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Wang, L., Ma, L., Fan, H. et al. MicroRNA-9 regulates cardiac fibrosis by targeting PDGFR-β in rats. J Physiol Biochem 72, 213–223 (2016). https://doi.org/10.1007/s13105-016-0471-y

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  • DOI: https://doi.org/10.1007/s13105-016-0471-y

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