Key result
miR-21 inhibition improves heart function and fibrosis in rat MI models via Jagged1.
Inhibition of miR-21 attenuates cardiac fibroblast-to-myofibroblast transformation and myocardial fibrosis post-MI by targeting Jagged1 in a rat model.
Caution against clinical translation of miR-21 inhibition post-MI; leaves open validation of the Jagged1 axis in human fibrosis models.
Myocardial fibrosis after myocardial infarction (MI) is a leading cause of heart diseases. MI activates cardiac fibroblasts (CFs) and promotes CF to myofibroblast transformation (CMT). This study aimed to investigate the role of miR-21 in the regulation of CMT and myocardial fibrosis. Primary rat CFs were isolated from young SD rats and treated with TGF-β1, miR-21 sponge or Jagged1 siRNA. Cell proliferation, invasion and adhesion were detected. MI model was established in male SD rats using LAD ligation method and infected with recombinant adenovirus. The heart function and morphology was evaluated by ultrasonic and histological analysis. We found that TGF-β1 induced the up-regulation of miR-21 and down-regulation of Jagged1 in rat CFs. Luciferase assay showed that miR-21 targeted 3'-UTR of Jagged1 in rat CFs. miR-21 sponge inhibited the transformation of rat CFs into myofibroblasts, and abolished the inhibition of Jagged1 mRNA and protein expression by TGF-β1. Furthermore, these effects of miR-21 sponge on rat CFS were reversed by siRNA mediated knockdown of Jagged1. In vivo, heart dysfunction and myocardial fibrosis in MI model rats were partly improved by miR-21 sponge but were aggravated by Jagged1 knockdown. Taken together, these results suggest that miR-21 promotes cardiac fibroblast-to-myofibroblast transformation and myocardial fibrosis by targeting Jagged1. miR-21 and Jagged1 are potential therapeutic targets for myocardial fibrosis.
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Zhou et al. (2018) studied Myocardial fibrosis after myocardial infarction. miR-21 sponge and Jagged1 siRNA was evaluated on Heart function, morphology, and cardiac fibroblast-to-myofibroblast transformation. Inhibition of miR-21 with a sponge improved heart dysfunction and myocardial fibrosis in a rat myocardial infarction model, an effect that was reversed by Jagged1 knockdown.
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