2. Academic Validation
  3. Peroxiredoxin-1 aggravates hypoxia-induced renal injury by promoting inflammation through the TLR4/MAPK/NF-κB signaling pathway

Peroxiredoxin-1 aggravates hypoxia-induced renal injury by promoting inflammation through the TLR4/MAPK/NF-κB signaling pathway

  • Free Radic Biol Med. 2025 Aug 16:236:176-187. doi: 10.1016/j.freeradbiomed.2025.05.399.
Yuanyuan Han 1,  Songkai Wang 1,  Yiwei Xiong 1,  Sha Tu 2,  Zujian Xiong 3,  Shenglan Li 4,  Wenzhe She 5,  Yan Zhang 1,  Xin He 1,  Sijue Zou 1,  Jiawei Cheng 1,  Jie Meng 6,  Qiongjing Yuan 1,  Ling Huang 1,  Yanyun Xie 1,  Lijian Tao 1,  Zhangzhe Peng 7
Affiliations

Affiliations

  • 1 Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Key Laboratory of Organ Fibrosis of Hunan Province, Central South University, Changsha, Hunan, China.
  • 2 Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China.
  • 3 Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 4 Key Laboratory of Organ Fibrosis of Hunan Province, Central South University, Changsha, Hunan, China; Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 5 Key Laboratory of Organ Fibrosis of Hunan Province, Central South University, Changsha, Hunan, China; Department of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan, China.
  • 6 Key Laboratory of Organ Fibrosis of Hunan Province, Central South University, Changsha, Hunan, China; Department of Respiratory Medicine, The 3rd Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 7 Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Key Laboratory of Organ Fibrosis of Hunan Province, Central South University, Changsha, Hunan, China. Electronic address: pengzhangzhe@csu.edu.cn.
PMID: 40398686 DOI: 10.1016/j.freeradbiomed.2025.05.399
Abstract

Hypoxia can induce pathological alterations to the kidneys, such as activation of inflammatory signaling pathways. This form of inflammation is pathogen-free and is referred to as aseptic inflammation. Currently, the mechanisms leading to aseptic inflammation under hypoxia are not well understood. Emerging evidence has indicated that Prdx1, a member of the peroxidase family, contributes to the development of various diseases by stimulating aseptic inflammation. This study was conducted to reveal the potential role of Prdx1 in the pathogenesis of hypoxia-induced renal injury. A mouse model of systemic hypoxia was developed, which revealed that Prdx1 levels were elevated in injured kidneys and peripheral circulation. A comparable increase was also observed in hypoxia-treated immortalized bone marrow-derived macrophages (iBMDM). Knock-down of Prdx1 in mice caused a significant reduction in renal tissue injury and inflammation induced by hypoxic injury. In addition, we demonstrated that Prdx1 modulates inflammatory responses by activating the TLR4/MAPK/NF-κB signaling pathways. Recombinant Prdx1 promoted the activation of these pathways in macrophages, whereas genetic knockout of Prdx1 or pharmacological inhibition suppressed their activity. Altogether, we found a previously unrecognized role for Prdx1 in the regulation of inflammation in hypoxia-induced renal injury. These findings suggest that Prdx1 can be a potential target for treating this severe disease.

Keywords

Hypoxia kidney injury; Inflammation; MAPK; NF-κB; Peroxiredoxin-1; TLR4.

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