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MicroRNA-214 Mediates Isoproterenol-induced Proliferation and Collagen Synthesis in Cardiac Fibroblasts.

Authors: Sun, M  Yu, H  Zhang, Y  Li, Z  Gao, W 
Citation: Sun M, etal., Sci Rep. 2015 Dec 22;5:18351. doi: 10.1038/srep18351.
Pubmed: (View Article at PubMed) PMID:26692091
DOI: Full-text: DOI:10.1038/srep18351

The action of beta-adrenergic receptors (beta-ARs) induces cardiac fibroblast (CF) proliferation and collagen synthesis and is a major source of the cardiac fibrosis caused by various diseases. Recently, microRNA-214 (miR-214) was found to play an important role in the pathogenesis of cardiac remodelling. In the present study, we examined the role and the underlying mechanism of miR-214 in isoproterenol (ISO, a beta-AR agonist)-induced CF proliferation and collagen synthesis. The expression of miR-214 was increased in both ISO-mediated fibrotic heart tissue and fibroblasts. Downregulation of miR-214 by antagonists attenuated the proliferation and collagen synthesis in ISO-treated CFs. Using bioinformatics analysis and luciferase assays, mitofusin2 (Mfn2), a critical regulator of cell proliferation and tissue fibrosis, was identified as a direct target gene of miR-214; this result was confirmed by western blot analysis. Additionally, corresponding to the upregulation of miR-214, the expression of Mfn2 was downregulated in the fibrotic heart and fibroblasts. Furthermore, the downregulation of miR-214 inhibited the activation of ERK1/2 MAPK signalling induced by ISO treatment. In conclusion, our study demonstrated that miR-214 mediates CF proliferation and collagen synthesis via inhibition of Mfn2 and activation of ERK1/2 MAPK signalling, which provides a new explanation for the mechanism of beta-AR activation-induced cardiac fibrosis.

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CRRD Object Information
CRRD ID: 11557238
Created: 2016-11-02
Species: All species
Last Modified: 2016-11-02
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.