Journal
FRONTIERS IN MOLECULAR BIOSCIENCES
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2021.789927
Keywords
ischemia-reperfusion; ferroptosis; acute kidney injury; heme oxygenase-1; microRNA
Categories
Funding
- National Natural Science Foundation of China [81871548]
- Key Research and Development Program of Jiangxi Province [20161BBG70173]
- Special Fund Project for Postgraduates Innovation of Jiangxi Province [YC2020-B050]
- Science and Technology Program of Health Commission of Jiangxi Province [20204033]
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This study investigated the miRNA-mRNA regulatory networks involved in ferroptosis following renal ischemia-reperfusion injury. The results showed that inhibition of miR-3587 promotes upregulation of HO-1, thereby protecting renal tissues from IR-induced ferroptosis.
Renal ischemia-reperfusion (IR) is frequently observed in patients who are critically ill, yet there are no reliable or effective approaches for the treatment of this condition. Ferroptosis, a form of programmed cell death, is regulated by key genes such as glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HMOX1) and participates in the injury of renal tubular epithelial cells during IR. This study aimed to investigate the miRNA-mRNA regulatory networks involved in ferroptosis following renal IR. Using bioinformatics analysis, HMOX1 was found to be significantly upregulated during the early stages of renal IR injury, and microRNA-3587 (miR-3587) was identified as a putative regulator of HMOX1. When a miR-3587 inhibitor was applied in a hypoxia-reoxygenation (HR) model system using renal tubular epithelial cells, HO-1 protein (encoded by HMOX1) expression was significantly increased relative to that observed in the HR group, with concomitant increases in GPX4 protein levels, enhanced cell viability, a reduction in malondialdehyde content, decreased Fe2+ level, and the restoration of normal mitochondrial membrane potential. Transmission electron microscopy showed a reduced or absent mitochondrial crest and a damaged mitochondrial outer membrane. Targeting of HMOX1 by miR-3587 was confirmed by luciferase reporter gene assay. In conclusion, these preliminary results indicate that inhibition of miR-3587 promotes HO-1 upregulation, thereby protecting renal tissues from IR-induced ferroptosis.
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