Exosomes derived from ADSC suppress endothelial cells ferroptosis and alleviate sepsis acute liver injury via regulation of Keap1/Nrf2/GPX4 axis: an experimental study.

IF 3.6 2区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

STEM CELLS Pub Date : 2025-09-27 DOI:10.1093/stmcls/sxaf063

Xianqi Wang, Dan Wu, Xiaoyang Liu, Yanan Xu, Peiwen Wang, Heliang Fu, Yuexiang Ma, Shanshou Liu, Qianmei Wang, Xian-Jie Xu, Zheng Dai, Qi Zhang, Wen Yin, Kuo Shen, Junjie Li

{"title":"Exosomes derived from ADSC suppress endothelial cells ferroptosis and alleviate sepsis acute liver injury via regulation of Keap1/Nrf2/GPX4 axis: an experimental study.","authors":"Xianqi Wang, Dan Wu, Xiaoyang Liu, Yanan Xu, Peiwen Wang, Heliang Fu, Yuexiang Ma, Shanshou Liu, Qianmei Wang, Xian-Jie Xu, Zheng Dai, Qi Zhang, Wen Yin, Kuo Shen, Junjie Li","doi":"10.1093/stmcls/sxaf063","DOIUrl":null,"url":null,"abstract":"Background: Adipose-derived stem cells exosome (ADSC-exo) has been reported to be effective in alleviating organ dysfunction in sepsis, including acute liver injury (ALI). Whether ADSC-exo protects the liver via suppression of vascular endothelial cell (VEC) ferroptosis is unclear.Methods: We evaluated the viability and migration of VECs and their ferroptosis-related indices. To further elucidate this mechanism, we examined the Nrf2/GPX4 pathway. Cecal ligation and puncture (CLP) was performed to establish a sepsis model to observe the protective effect of ADSC-exo. The death rate and liver tissue injury were observed. We also evaluated inflammation- and ferroptosis-related indices. Next, we examined the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) pathway-related molecules to elucidate the underlying mechanism.Results: ADSC-exo reduced cell injury and ferroptosis in VECs. ADSC-exo increased the expression and nuclear translocation of Nrf2. In the CLP-induced sepsis model, ADSC-exo relieved liver injury and reduced the death rate. Further observations showed that ADSC-exo significantly alleviated oxidative stress injury and ferroptosis in liver tissue, while remarkably increasing the expression of Nrf2 and GPX4.Conclusion: These findings demonstrate the remarkable ability of ADSC-exo to alleviate sepsis-induced ALI by mitigating endothelial cell ferroptosis, providing evidence for the potential clinical application of ADSC-exo in ALI therapy.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"STEM CELLS","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/stmcls/sxaf063","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Adipose-derived stem cells exosome (ADSC-exo) has been reported to be effective in alleviating organ dysfunction in sepsis, including acute liver injury (ALI). Whether ADSC-exo protects the liver via suppression of vascular endothelial cell (VEC) ferroptosis is unclear.

Methods: We evaluated the viability and migration of VECs and their ferroptosis-related indices. To further elucidate this mechanism, we examined the Nrf2/GPX4 pathway. Cecal ligation and puncture (CLP) was performed to establish a sepsis model to observe the protective effect of ADSC-exo. The death rate and liver tissue injury were observed. We also evaluated inflammation- and ferroptosis-related indices. Next, we examined the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) pathway-related molecules to elucidate the underlying mechanism.

Results: ADSC-exo reduced cell injury and ferroptosis in VECs. ADSC-exo increased the expression and nuclear translocation of Nrf2. In the CLP-induced sepsis model, ADSC-exo relieved liver injury and reduced the death rate. Further observations showed that ADSC-exo significantly alleviated oxidative stress injury and ferroptosis in liver tissue, while remarkably increasing the expression of Nrf2 and GPX4.

Conclusion: These findings demonstrate the remarkable ability of ADSC-exo to alleviate sepsis-induced ALI by mitigating endothelial cell ferroptosis, providing evidence for the potential clinical application of ADSC-exo in ALI therapy.

查看原文本刊更多论文

ADSC来源的外泌体通过调控Keap1/Nrf2/GPX4轴抑制内皮细胞铁下沉，减轻脓毒症急性肝损伤的实验研究

背景：据报道，脂肪源性干细胞外泌体（ADSC-exo）可有效缓解脓毒症患者的器官功能障碍，包括急性肝损伤（ALI）。ADSC-exo是否通过抑制血管内皮细胞（VEC）铁下垂来保护肝脏尚不清楚。方法：评价VECs的生存能力、迁移能力及相关指标。为了进一步阐明这一机制，我们研究了Nrf2/GPX4通路。采用盲肠结扎穿刺法（CLP）建立脓毒症模型，观察ADSC-exo的保护作用。观察死亡率及肝组织损伤情况。我们还评估了炎症和死铁相关指标。接下来，我们检测核因子红细胞2相关因子2 (Nrf2)/谷胱甘肽过氧化物酶4 （GPX4）通路相关分子的表达，以阐明其潜在机制。结果：ADSC-exo可减轻vec细胞损伤和铁下垂。ADSC-exo增加Nrf2的表达和核易位。在clp诱导的脓毒症模型中，ADSC-exo可减轻肝损伤，降低死亡率。进一步观察发现，ADSC-exo显著减轻肝组织氧化应激损伤和铁下垂，同时显著增加Nrf2和GPX4的表达。结论：这些发现表明ADSC-exo通过减轻内皮细胞铁下垂来减轻脓毒症诱导的ALI，为ADSC-exo在ALI治疗中的潜在临床应用提供了证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

STEM CELLS 医学-生物工程与应用微生物

CiteScore

10.30

自引率

1.90%

发文量

104

审稿时长

3 months

期刊介绍： STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. STEM CELLS is read and written by clinical and basic scientists whose expertise encompasses the rapidly expanding fields of stem and progenitor cell biology. STEM CELLS covers: Cancer Stem Cells, Embryonic Stem Cells/Induced Pluripotent Stem (iPS) Cells, Regenerative Medicine, Stem Cell Technology: Epigenetics, Genomics, Proteomics, and Metabonomics, Tissue-Specific Stem Cells, Translational and Clinical Research.