miR-3587 Inhibitor Attenuates Ferroptosis Following Renal Ischemia-Reperfusion Through HO-1

被引:32
作者
Tao, Wenqiang [1 ,2 ]
Liu, Fen [1 ]
Zhang, Jianguo [3 ]
Fu, Shangmiao [1 ]
Zhan, Hui [1 ]
Qian, Kejian [1 ]
机构
[1] Nanchang Univ, Dept Intens Care Med, Affiliated Hosp 1, Nanchang, Peoples R China
[2] Nanchang Univ, Affiliated Hosp 1, Med Innovat Ctr, Nanchang, Peoples R China
[3] Nanchang Univ, Affiliated Hosp 1, Dept Infect, Nanchang, Peoples R China
基金
中国国家自然科学基金;
关键词
ischemia-reperfusion; ferroptosis; acute kidney injury; heme oxygenase-1; microRNA; CELL-DEATH; GENE-EXPRESSION; KIDNEY; IDENTIFICATION; INJURY;
D O I
10.3389/fmolb.2021.789927
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
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页数:11
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