MiR-30e Attenuates Isoproterenol-induced Cardiac Fibrosis Through Suppressing Snai1/TGF-β Signaling

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Abstract

Background:

MicroRNAs are a class of small RNA molecules that inhibit protein expression through either degradation of messenger RNA or interference with protein translation. Our previous work suggested an involvement of miR-30e in myocardial fibrosis; however, the exact role of miR-30e in the pathogenesis of cardiac fibrosis and the underlying mechanisms are not known.

Methods:

Male Sprague Dawley rats were treated with isoproterenol (ISO) to induce cardiac remodeling and fibrosis and treated with either miR-30e agomir (AG) or antagomir and respective controls. The expression of miR-30e was evaluated by reverse transcription and quantitative polymerase chain reaction. Myocardial fibrosis was assessed by Masson's trichrome staining, and the level of oxidative stress and the expression of Snai1 and transforming growth factor-beta (TGF-β) were detected using Western blots.

Results:

A significant downregulation of miR-30e was found in the hearts of ISO-treated rats with cardiac fibrosis compared with nontreated controls. In vivo administration of miR-30e AG increased the survival of ISO-treated rats compared with AG-negative control administration, which was associated with reduced oxidative stress. We further identified Snai1 as a novel miR-30e target. Snai1 expression was significantly increased in hearts from ISO-treated rats, which coincided with decreased miR-30e expression and increased TGF-β expression. An miR-30e putative target sequence was identified in the 3′-untranslated region (UTR) Snai1. In a reporter assay, miR-30e greatly suppressed the activity of wild-type 3′-UTR–fused luciferase reporter, but showed no significant effect with the mutated 3′-UTR–fused reporter.

Conclusion:

MiR-30e attenuated ISO-induced cardiac dysfunction and cardiac fibrosis in a rat cardiac remodeling model. Mechanistically, miR-30e suppressed Snai1/TGF-β pathway which was involved in ISO-induced cardiac remodeling.

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