miR-3587 Inhibitor Attenuates Ferroptosis Following Renal Ischemia-Reperfusion Through HO-1
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 o...
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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.789927/full |
| _version_ | 1819098308793073664 |
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| author | Wenqiang Tao Wenqiang Tao Fen Liu Jianguo Zhang Shangmiao Fu Hui Zhan Kejian Qian |
| author_facet | Wenqiang Tao Wenqiang Tao Fen Liu Jianguo Zhang Shangmiao Fu Hui Zhan Kejian Qian |
| author_sort | Wenqiang Tao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T00:28:56Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-22T00:28:56Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-abfec25bd2414f50a3996b5460e74a162022-12-21T18:44:59ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-01-01810.3389/fmolb.2021.789927789927miR-3587 Inhibitor Attenuates Ferroptosis Following Renal Ischemia-Reperfusion Through HO-1Wenqiang Tao0Wenqiang Tao1Fen Liu2Jianguo Zhang3Shangmiao Fu4Hui Zhan5Kejian Qian6Department of Intensive Care Medicine, First Affiliated Hospital of Nanchang University, Nanchang, ChinaMedical Innovation Center, First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Intensive Care Medicine, First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Infection, First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Intensive Care Medicine, First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Intensive Care Medicine, First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Intensive Care Medicine, First Affiliated Hospital of Nanchang University, Nanchang, ChinaRenal 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.https://www.frontiersin.org/articles/10.3389/fmolb.2021.789927/fullischemia-reperfusionferroptosisacute kidney injuryheme oxygenase-1microRNA |
| spellingShingle | Wenqiang Tao Wenqiang Tao Fen Liu Jianguo Zhang Shangmiao Fu Hui Zhan Kejian Qian miR-3587 Inhibitor Attenuates Ferroptosis Following Renal Ischemia-Reperfusion Through HO-1 Frontiers in Molecular Biosciences ischemia-reperfusion ferroptosis acute kidney injury heme oxygenase-1 microRNA |
| title | miR-3587 Inhibitor Attenuates Ferroptosis Following Renal Ischemia-Reperfusion Through HO-1 |
| title_full | miR-3587 Inhibitor Attenuates Ferroptosis Following Renal Ischemia-Reperfusion Through HO-1 |
| title_fullStr | miR-3587 Inhibitor Attenuates Ferroptosis Following Renal Ischemia-Reperfusion Through HO-1 |
| title_full_unstemmed | miR-3587 Inhibitor Attenuates Ferroptosis Following Renal Ischemia-Reperfusion Through HO-1 |
| title_short | miR-3587 Inhibitor Attenuates Ferroptosis Following Renal Ischemia-Reperfusion Through HO-1 |
| title_sort | mir 3587 inhibitor attenuates ferroptosis following renal ischemia reperfusion through ho 1 |
| topic | ischemia-reperfusion ferroptosis acute kidney injury heme oxygenase-1 microRNA |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.789927/full |
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