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Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury

文献类型：期刊论文

作者He, Yao1,2; Yang, Xue1,2,3; Zhang, Chenyu1,2; Deng, Min1,2,3; Tu, Bin4; Liu, Qian1,2; Cai, Jiaying1,2; Zhang, Ying1,2,5; Su, Li6; Yang, Zhiwen1,2,5
刊名ACTA PHARMACEUTICA SINICA B
出版日期2025-06-01
卷号15期号:6页码:3107-3124
关键词AKI I/R injury FoxO1 Macrophage Chemotaxis Inflammation Migration ARHGEF1
ISSN号2211-3835
DOI10.1016/j.apsb.2025.04.009
英文摘要Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI. 2025 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
WOS关键词NLRP3 INFLAMMASOME ; EPITHELIAL-CELLS ; POLARIZATION ; FIBROSIS ; DISEASE ; MODEL ; PROGRESSION ; MIGRATION ; PROTEINS ; ADHESION
资助项目National Natural Science Foundation of China[82073878] ; National Natural Science Foundation of China[81874318] ; National Natural Science Foundation of China[81473235]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001521723100002
出版者INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
源URL[http://119.78.100.183/handle/2S10ELR8/321081]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Li, Linlin; Zhang, Long; Huang, Yongzhuo; Tie, Lu
作者单位1.Peking Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing 100191, Peoples R China
2.Peking Univ, Beijing Key Lab Tumor Syst Biol, Beijing 100191, Peoples R China
3.Xinjiang Med Univ, Dept Pharmacol, Urumqi 830011, Xinjiang, Peoples R China
4.Guangzhou Univ Tradit Chinese Med, Zhongshan Hosp Tradit Chinese Med, Zhongshan 528400, Peoples R China
5.Peking Univ Hosp 3, Dept Wound Healing Ctr & Intervent Radiol & Vasc S, Dept Intervent Radiol & Vasc Surg, Beijing 100191, Peoples R China
6.Peking Univ, Med & Hlth Anal Ctr, Beijing 100191, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 He, Yao,Yang, Xue,Zhang, Chenyu,et al. Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury[J]. ACTA PHARMACEUTICA SINICA B,2025,15(6):3107-3124.
APA He, Yao.,Yang, Xue.,Zhang, Chenyu.,Deng, Min.,Tu, Bin.,...&Tie, Lu.(2025).Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury.ACTA PHARMACEUTICA SINICA B,15(6),3107-3124.
MLA He, Yao,et al."Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury".ACTA PHARMACEUTICA SINICA B 15.6(2025):3107-3124.

入库方式： OAI收割

来源：上海药物研究所

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