Abstract 167: Mir-195-3p/-5p Decrease Cardiac Fibroblast Proliferation and the Transdifferentiation into Myofibroblasts

Aims: MicroRNAs (miRNAs, miRs) contribute to many essential physiological and pathological processes including fibrosis. This study aims at investigating the role of miR-195-3p/-5p in cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts. Methods and results: In isolated primary neonatal cardiac fibrobasts (NRCFs), forced expression of miR-195-3p/-5p with agomiRs could attenuate fibrobast proliferation as determined by EdU and Ki67 staining while inhibition of miR-195-3p/-5p with antagomiRs could increase fibrobast proliferation. By quantitative reverse transcription polymerase chain reactions (RT-PCRs) and western blotting (WB), α-SMA (a marker of myofibroblast transdifferentiation) was found to be suppressed in the miR-195-3p/-5p agomiR-treated NRCFs at both mRNA and protein levels, while was increased in the miR-195-3p/-5p antagomiR-treated NRCFs. Moreover, Chek-1 was identified as a target gene of miR-195-3p/-5p responsible for cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts by RT-PCR and WB and immunofluorescent staining. Silencing of Chek-1 attenuates cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts as detected by α-SMA/EDU staining. In addition, Chek-1 mediated the effects of miR-195-3p/-5p in cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts. Conclusion: Therefore, miR-195-3p/-5p might be promising therapeutic targets for cardiac fibrosis.