Selenoprotein GPX3 regulates NADPH oxidase expression by inhibiting the MAPK signaling pathway and thereby attenuating the inflammatory response in renal ischemia-reperfusion injury

Sep 29, 2026

Uploaded by Franzy

Renal ischemia-reperfusion injury (IRI) is a major driver of acute kidney injury, with inflammation serving as a key pathogenic factor. The selenoprotein GPX3, a glutathione peroxidase family member, is linked to anti-inflammatory effects, yet its role in renal IRI and underlying mechanisms remained unclear. Using rat kidney IRI and hypoxia-reoxygenation models, GPX3 overexpression reduced inflammatory factor expression, increased IL-10, and alleviated renal IRI. Mechanistically, GPX3 reduced NADPH oxidase expression by inhibiting MAPK signaling.

LanguageEnglish

CategoryHealthcare

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Abstract

Introduction

Acute kidney injury and renal ischemia-reperfusion injury

Inflammatory mechanisms in AKI

Mechanistic rationale for GPX3 in renal IRI

Genes & Diseases (2026) 13, 101640 Available online [at](at www.sciencedirect.com)[ www.sciencedirect.com](at www.sciencedirect.com) ScienceDirect journal [homepage:](homepage: www. keaipublishing. com/en/journals/genes-diseases)[ www. keaipublishing. com/en/journals/genes-diseases](homepage: www. keaipublishing. com/en/journals/genes-diseases) FULL LENGTH ARTICLE Selenoprotein GPX3 regulates NADPH oxidase expression by inhibiting the MAPK signaling pathway and thereby attenuating the inﬂammatory response in renal ischemia-reperfusion injury Jun Pei a,b,c, Jie Zhang a,b,c, Chengjun Yu a,b,c, Jin Luo a,b,c, Sheng Wen a,b,c, Yi Hua a,b,c,* , Guanghui Wei a,b,c,** a Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China b Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China c Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, China Received 31 October 2024; received in revised form 24 February 2025; accepted 6 March 2025 Available online 11 April 2025 KEYWORDS GPX3; Inﬂammation; Ischemia-reperfusion injury; Kidney; Selenoprotein Abstract Renal ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney injury, and the inﬂammatory response is considered a key factor. The selenoprotein GPX3, a member of the glutathione peroxidase family, has gradually attracted attention for its anti-inﬂammatory properties. However, the relationship between GPX3 and the inﬂammatory response during renal IRI remains unclear. The present study aims to investigate the role of GPX3 on the inﬂammatory response during renal IRI and related mechanisms. We utilized classic rat models of kidney IRI and cellular hypoxia reoxygenation model. After overexpressing GPX3 via lentiviruses and adeno-associated viruses, we observed a signiﬁcant reduction in the expression levels of inﬂammatory factors in renal tissues, along with an increase in the expression of anti-inﬂammatory factor IL-10, resulting in noticeable alleviation of renal IRI. Meanwhile, we found that GPX3 alleviated the inﬂammatory response, probably by inhibiting the MAPK signaling pathway and reducing the expression of NAPDH oxidase. To further validate * Corresponding author. Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China. ** Corresponding author. Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China. E-mail addresses: [400137@cqmu.edu.cn](400137@cqmu.edu.cn) (Y. Hua), [u806806@cqmu.edu.cn](u806806@cqmu.edu.cn) (G. Wei). Peer review under the responsibility of Chongqing Medical University. [https://doi.org/10.1016/j.gendis.2025.101640](https://doi.org/10.1016/j.gendis.2025.101640) 2352-3042/ª 2025 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY license ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)). the mechanism by which GPX3 alleviated the inﬂammatory response, we used the MAPK signaling pathway agonist anisomycin for intervention. The results showed that anisomycin intervention signiﬁcantly reversed the inhibitory effect of GPX3 on the MAPK signaling pathway, in which the expression level of NADPH oxidase was signiﬁcantly increased, the secretion of inﬂammatory factors was increased, and the degree of renal tissue damage was signiﬁcantly increased. These ﬁndings suggest that selenoprotein GPX3 alleviates inﬂammation during renal IRI by inhibiting the MAPK signaling pathway and reducing NADPH oxidase expressi

FAQs

What is the main research question of the study?

The study investigates how selenoprotein GPX3 influences the inflammatory response during renal ischemia-reperfusion injury and through which mechanisms.

How was GPX3 tested in the experiments?

GPX3 was overexpressed using lentiviral and adeno-associated viral approaches in classic rat kidney IRI models and cellular hypoxia-reoxygenation models.

What mechanism links GPX3 to reduced inflammation in renal IRI?

GPX3 alleviated inflammation by inhibiting the MAPK signaling pathway, which reduced NADPH oxidase expression and lowered inflammatory factor production.

How did the MAPK pathway agonist anisomycin affect the findings?

Anisomycin reversed GPX3’s inhibitory effects on MAPK signaling, increasing NADPH oxidase levels, inflammatory factor secretion, and renal tissue damage.

Sep 29, 2026

Uploaded by Franzy