Jiao Chen, Li Hengyi, Wu Yongdong, Hu Lemei, Huang Fengzhang, Liang Ming
Department of Nephrology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, PR China.
School of Medicine, South China University of Technology, Guangzhou, PR China.
Ren Fail. 2025 Dec;47(1):2509802. doi: 10.1080/0886022X.2025.2509802. Epub 2025 Jun 8.
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.
An 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.
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.
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.
先前的研究表明，用抗氧化剂S-PPE纳米颗粒治疗急性肾损伤（AKI）可降低氧化应激反应蛋白Sestrin2（SESN2）的水平，并提示肾损伤分子1（KIM-1）可作为早期肾小管损伤的生物标志物。全面阐明S-PPE纳米颗粒对缺血再灌注损伤性急性肾损伤（IRI-AKI）中SESN2和KIM-1表达的调节作用，可能会增强AKI的治疗方法。
利用人肾-2（HK-2）细胞缺氧/复氧（H/R）模型和小鼠IRI模型，在不同时间点评估SESN2和KIM-1的表达，并评估S-PPE纳米颗粒治疗的影响。还证实了SESN2/AMPK/KIM-1信号通路的功能。
在H/R和IRI模型中均观察到SESN2和KIM-1的显著上调，S-PPE纳米颗粒治疗后这种上调减弱。SESN2的过表达导致AMPK磷酸化增强和KIM-1水平降低，而用化合物C抑制AMPK磷酸化不影响SESN2水平，但导致KIM-1水平升高。
SESN2在肾IRI-AKI的初始阶段作为一种保护因子，通过促进AMPK磷酸化来促进肾脏修复，进而抑制KIM-1表达。此外，S-PPE纳米颗粒通过直接清除活性氧和降低SESN2表达有效地减轻IRI-AKI。
