Direct scavenging of ROS by S-PPE NP reduces oxidative stress-induced stimulation of the SESN2/AMPK/KIM-1 pathway in acute kidney injury
Background Previous research demonstrated that treatment of acute kidney injury (AKI) with the antioxidant S-PPE NP reduced the levels of the oxidative stress-responsive protein Sestrin2 (SESN2), and suggested that kidney injury molecule 1 (KIM-1) could serve as a biomarker for early tubular injury....
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
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| Series: | Renal Failure |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2025.2509802 |
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| Summary: | Background Previous research demonstrated that treatment of acute kidney injury (AKI) with the antioxidant S-PPE NP reduced the levels of the oxidative stress-responsive protein Sestrin2 (SESN2), and suggested that kidney injury molecule 1 (KIM-1) could serve as a biomarker for early tubular injury. A comprehensive elucidation of the regulatory effects of S-PPE NP on SESN2 and KIM-1 expression in ischemia-reperfusion injury-AKI (IRI-AKI) could enhance therapeutic approaches for AKI.Materials and methods An in vitro human kidney-2 (HK-2) cell hypoxia/reoxygenation (H/R) model and a mouse IRI model were utilized at various time points to assess the expression of SESN2 and KIM-1 and to evaluate the impact of S-PPE NP treatment. The functionality of the SESN2/AMPK/KIM-1 signaling pathway was also confirmed.Results Significant upregulation of SESN2 and KIM-1 was observed in both H/R and IRI models, which was attenuated following S-PPE NP treatment. Overexpression of SESN2 resulted in enhanced AMPK phosphorylation and reduced KIM-1 levels, whereas inhibition of AMPK phosphorylation with compound C did not affect SESN2 levels but led to an increase in KIM-1 levels.Conclusion SESN2 serves as a protective factor in the initial phase of renal IRI-AKI, facilitating renal repair by promoting AMPK phosphorylation, which subsequently suppresses KIM-1 expression. Moreover, S-PPE NPs effectively mitigate IRI-AKI by directly scavenging reactive oxygen species and reducing SESN2 expression. |
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| ISSN: | 0886-022X 1525-6049 |