Abstract
Although miR-327 had a protective effect on cardiomyocytes as described previously, the potential mechanism still needs further exploration. The aim of this study was to investigate the role and mechanism of miR-327 on oxidative stress in myocardial ischemia/reperfusion injury (MI/RI) process. Oxidative stress and cardiomyocytes injury were detected in rat model of MI/RI, hypoxia/reoxygenation (H/R), and tert-butyl hydroperoxide (TBHP) model of H9c2 cells. In vitro, downregulation of miR-327 inhibited both H/R- and TBHP-induced oxidative stress, and suppressed apoptosis. Meanwhile, fibroblast growth factor 10(FGF10) was enhanced by miR-327 knocked down, followed by the activation of p-PI3K and p-Akt, and the translocation of Nrf2. However, miR-327 overexpression performed with opposite effects. Consistent with the results in vitro, downregulation of miR-327 attenuated reactive oxygen species (ROS) generation as well as intrinsic apoptosis, and alleviated I/R injury. In conclusion, inhibition of miR-327 improved antioxidative ability and myocardial cell survival via regulating the FGF10/Akt/Nrf2 pathway.
Highlights
Rapid reperfusion therapy can effectively restore the oxygen and nutrient supply in the ischemic area and avoid further degeneration of the infarcted myocardium in ischemic heart disease (IHD) patients (Anderson and Morrow, 2017)
Inflammation, excessive reactive oxygen species (ROS), apoptosis, and other pathological can happen in the reperfusion area, which indicates that myocardial ischemia reperfusion injury (MIRI) occurred (SanchezHernandez et al, 2020)
We demonstrated that miR-327 participated in oxidative stress induced by myocardial I/R both in vivo and in vitro
Summary
Rapid reperfusion therapy can effectively restore the oxygen and nutrient supply in the ischemic area and avoid further degeneration of the infarcted myocardium in ischemic heart disease (IHD) patients (Anderson and Morrow, 2017). Some miRNAs have been reported to mediate oxidative stress through directly targeting antioxidant genes (e.g., Trx and Sirt) or indirectly interfering with prosurvival signaling pathways (e.g., Akt and IGF-1) and redox transcription factors (e.g., p53, NF-κB, and Nfr2) (Lin, 2019; Climent et al, 2020). It is well known that the excessive ROS is a key factor in the initiation of intrinsic apoptosis (Hossain et al, 2020). Fischer et al demonstrated that FGF10, as a target gene of miR-327, inhibits the FGF10-triggered fibroblast growth factor receptor (FGFR)–Akt signaling axis in the white fat browning study (Fischer et al, 2017). Whether miR-327 can regulate the FGF10/Akt signaling pathway participated in oxidative stress of MIRI is far from clear yet
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