ArticleJCI insight2022
Modulation of gentamicin-induced acute kidney injury by myo-inositol oxygenase via the ROS/ALOX-12/12-HETE/GPR31 signaling pathway.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Pla2g7 regulates bone homeostasis via Alox12/12-HETE/Gpr31 signaling axis.Nature communications · 2025Article
- Metformin alleviates renal tubular injury in diabetic kidney disease by activating mitophagy and inhibiting ferroptosis via HIF-1α/MIOX axis.Journal of pharmaceutical analysis · 2025Article
- Myo-Inositol Oxygenase (MIOX): A Pivotal Regulator and Therapeutic Target in Multiple Diseases.Current issues in molecular biology · 2025Review
- Multiparametric Evaluation of Drug-Induced Acute Kidney Injury Using Preclinical 7T Magnetic Resonance Imaging in Rat Models.Metabolites · 2025Article
- Direct Effects of Clinically Relevant Antibiotics on Mitochondrial Respiration.International journal of molecular sciences · 2025Article
- Nephroprotective Impacts ofFood science & nutrition · 2025Article
- Advances of Stimuli-Responsive Amphiphilic Copolymer Micelles in Tumor Therapy.International journal of nanomedicine · 2025Review
- Development and Validation of a Diagnostic Model for AKI Based on the Analysis of Ferroptosis-related Genes.Current medicinal chemistry · 2025Article
- Ivacaftor attenuates gentamicin-induced ototoxicity through the CFTR-Nrf2-HO1/NQO1 pathway.Redox report : communications in free radical research · 2024Article
- Exploring the role and therapeutic potential of lipid metabolism in acute kidney injury.Renal failure · 2024Review
- 12-HETE activates Müller glial cells: The potential role of GPR31 and miR-29.Prostaglandins & other lipid mediators · 2024Article
- Single cell multi-omics of fibrotic kidney reveal epigenetic regulation of antioxidation and apoptosis within proximal tubule.Cellular and molecular life sciences : CMLS · 2024Article
- Arachidonic acid metabolism as a therapeutic target in AKI-to-CKD transition.Frontiers in pharmacology · 2024Review
- Sustained activation of 12/15 lipoxygenase (12/15 LOX) contributes to impaired renal recovery post ischemic injury in male SHR compared to females.Molecular medicine (Cambridge, Mass.) · 2023Article
- Diacerein modulates TLR4/ NF-κB/IL-1β and TRPC1/CHOP signalling pathways in gentamicin-induced parotid toxicity in rats.Journal of cellular and molecular medicine · 2023Article
- Natural products for the prevention of antibiotic-associated kidney injury.Current opinion in toxicology · 2022Article
- Serum myo-inositol oxygenase levels at hospital discharge predict progression to chronic kidney disease in community-acquired acute kidney injury.Scientific reports · 2022Observational
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4 authors.
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Abstract
In this investigation, a potentially novel signaling pathway in gentamicin-induced acute kidney injury-worsened by overexpression of proximal tubular enzyme, myo-inositol oxygenase (MIOX)-was elucidated. WT, MIOX-transgenic (MIOX-Tg), and MIOX-KO mice were used. Gentamicin was administered to induce tubular injury. MIOX-Tg mice had severe tubular lesions associated with increased serum creatinine and proteinuria. Lesions were relatively mild, with no rise in serum creatinine and no albuminuria in MIOX-KO mice. Transfection of HK-2 cells with MIOX-pcDNA led to increased gentamicin-induced reactive oxygen species (ROS). Marked increase of ROS-mediated lipid hydroperoxidation was noted in MIOX-Tg mice, as assessed by 4-HNE staining. This was associated with increased expression of arachidonate 12-lipoxygenase (ALOX-12) and generation of 12-hydroxyeicosatetraenoic acid (12-HETE). In addition, notable monocyte/macrophage influx, upregulation of NF-κB and inflammatory cytokines, and apoptosis was observed in MIOX-Tg mice. Treatment of cells with ALOX-12 siRNA abolished gentamicin-mediated induction of cytokines and 12-HETE generation. HETE-12 treatment promoted this effect, along with upregulation of various signaling kinases and activation of GPCR31. Similarly, treatment of cells or mice with the ALOX-12 inhibitor ML355 attenuated inflammatory response, kinase signaling cascade, and albuminuria. Collectively, these studies highlight a potentially novel mechanism (i.e., the ROS/ALOX-12/12-HETE/GPR31 signaling axis) relevant to gentamicin-induced nephrotoxicity modulated by MIOX.
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