Cardiac fibroblast miR-27a may function as an endogenous anti-fibrotic by negatively regulating Early Growth Response Protein 3 (EGR3).

Journal of Cellular and Molecular Medicine
Lifeng TengQianqian Chen

Abstract

Pathological myocardial fibrosis and hypertrophy occur due to chronic cardiac stress. The microRNA-27a (miR-27a) regulates collagen production across diverse cell types and organs to inhibit fibrosis and could constitute an important therapeutic avenue. However, its impact on hypertrophy and cardiac remodelling is less well-known. We employed a transverse aortic constriction (TAC) murine model of left ventricular pressure overload to investigate the in vivo effects of genetic miR-27a knockout, antisense inhibition of miR-27a-5p and fibroblast-specific miR-27a knockdown or overexpression. In silico Venn analysis and reporter assays were used to identify miR-27a-5p's targeting of Early Growth Response Protein 3 (Egr3). We evaluated the effects of miR-27a-5p and Egr3 upon transforming growth factor-beta (Tgf-β) signalling and secretome of cardiac fibroblasts in vitro. miR-27a-5p attenuated TAC-induced cardiac fibrosis and myofibroblast activation in vivo, without a discernible effect on cardiac myocytes. Molecularly, miR-27a-5p inhibited transforming growth factor-beta (Tgf-β) signalling and pro-fibrotic protein secretion in cardiac fibroblasts in vitro through suppressing the pro-fibrotic transcription factor Early Growth Respons...Continue Reading

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Methods Mentioned

BETA
genetic knockout
PCR
transfection

Software Mentioned

Targetscan
Venn

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