Abstract
Our study aspires to understand the impact of miR-27b on myocardial fibrosis as well as its functional mechanism. 12 days post the ligation of coronary artery in rats, the expression of miR-27b in the peri-infarction region was elevated. Treating cultivated rat neonatal cardiac fibroblasts (CFs) with angiotensin II (AngII) also enhanced the miR-27b expression. Forced expression of miR-27b promoted the proliferation and collagen production in rat neonatal CFs, as revealed by cell counting, MTT assay, and quantitative reverse transcription-polymerase chain reaction. FBW7 was found to be the miR-27b’s target since the overexpression of miR-27b reduced the transcriptional level of FBW7. The enhanced expression of FBW7 protein abrogated the effects of miR-27b in cultured CFs, while the siRNA silence of FBW7 promoted the pro-fibrosis activity of AngII. As to the mechanism, we found that the expression of FBW7 led to the degradation of Snail, which is an important regulator of cardiac epithelial-mesenchymal transitions. Importantly, inhibition of miR-27b abrogated the coronary artery ligation (CAL) induced cardiac fibrosis in vivo, suggesting that it might be a potential target for the treatment of fibrosis associated cardiac diseases.
Highlights
The fibrotic formation is an important pathological characteristic linked to many types of cardiac disorders, such as myocardial infarction, myocardial ischemia, hypertrophic cardiomyopathies, and cardiac failure [1]
To investigate the role of miR-27 in the cardiac fibrosis, its expression in rat post-infarct cardiac tissues and cultured cardiac fibroblasts (CFs) was first detected under the conditions with significant CF proliferation
Cardiac fibrosis might be associated with unfavorable cardiovascular outcomes, since it plays a key role in cardiac remodeling [15]
Summary
The fibrotic formation is an important pathological characteristic linked to many types of cardiac disorders, such as myocardial infarction, myocardial ischemia, hypertrophic cardiomyopathies, and cardiac failure [1]. The fundamental of fibrotic formation is the adverse collection of collagen and extracellular matrix (ECM) proteins, which damage normal cardiac function and cause arrhythmia [2]. The fibrotic ECM leads to elevated rigidity and triggers pathological signals in cardiocytes, which result in heart failure. ECM, and upon activation they directly result in hypertrophic cardiomyocytes through paracrine principles, aggravating the impairment in heart functioning [3, 4]. Coupling of TGF-β with its cell-surface receptors signals, the Smad pathway mediates the transcriptional processes of some central fibrosis genes, such as fibronectin, collagens [7]. More efforts should be made to identify novel therapeutic targets for cardiac fibrosis
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