MicroRNA-24 regulates cardiac fibrosis after myocardial infarction.
Bottom Line: TGF-β (a pathological mediator of fibrotic disease) increased miR-24 expression, overexpression of miR-24 reduced TGF-β secretion and Smad2/3 phosphorylation in CFs.Finally, we demonstrated that protein and mRNA levels of furin were regulated by miR-24 in CFs.These findings suggest that miR-24 has a critical role in CF function and cardiac fibrosis after MI through a furin-TGF-β pathway.
Affiliation: State Key Laboratory of Translational Cardiovascular Medicine, Fuwai Hospital & Cardiovascular Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.Show MeSH
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Mentions: Global changes in the transcriptional profile of CFs over-expressing miR-24 were assessed by microarray (data not shown). By using the TargetScan and Sanger database and bioinformatics analyses, we identified furin as a highly likely miR-24 target to regulate the TGF-β1 pathway. Furin is a protease and has been reported to regulate TGF-β maturation. Through target prediction tools we identified one miR-24-conserved binding site in furin mRNA (Fig. 6C). Loss-of-function and gain-of-function experiments indicated that the transfected miR-24 precursors in CFs significantly down-regulated furin expression at protein and mRNA levels, whereas inhibition of miR-24 up-regulated furin expression (Fig. 6A and B). To detect the function of furin in CFs, we used siRNA of furin to inhibit it in CFs and detected the expression of furin, collagen-1 and α-SMA by qRT-PCR and western blotting. The results showed that furin was reduced significantly after transfection, and the expression of collagen-1 and α-SMA was also downregulated in protein and mRNA level (Fig. 6D and E). This means that furin may regulate the fibrosis level in CFs.
Affiliation: State Key Laboratory of Translational Cardiovascular Medicine, Fuwai Hospital & Cardiovascular Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.