在脊髓损伤中,白桦酸通过AMPK-HDAC5-KLF2信号通路增强自噬,促进小胶质细胞M2极化,减轻炎症

IF 4.7 2区 医学 Q2 IMMUNOLOGY
Zili He , Yitie Xu , Yu Zhang , Mengqi Jin , Yinuo Sun , Fangying Tang , Chuangqi Qiu , Abass Mashud Akinfemi Junior , Yunhao Cai , Xiaodan Xu , Xianghang Chen , Kongbin Chen , Guangheng Xiang , Jian Xiao , Jian Wang , Jing Wang , Baoyi Chen
{"title":"在脊髓损伤中,白桦酸通过AMPK-HDAC5-KLF2信号通路增强自噬,促进小胶质细胞M2极化,减轻炎症","authors":"Zili He ,&nbsp;Yitie Xu ,&nbsp;Yu Zhang ,&nbsp;Mengqi Jin ,&nbsp;Yinuo Sun ,&nbsp;Fangying Tang ,&nbsp;Chuangqi Qiu ,&nbsp;Abass Mashud Akinfemi Junior ,&nbsp;Yunhao Cai ,&nbsp;Xiaodan Xu ,&nbsp;Xianghang Chen ,&nbsp;Kongbin Chen ,&nbsp;Guangheng Xiang ,&nbsp;Jian Xiao ,&nbsp;Jian Wang ,&nbsp;Jing Wang ,&nbsp;Baoyi Chen","doi":"10.1016/j.intimp.2025.114889","DOIUrl":null,"url":null,"abstract":"<div><div>Spinal cord injury (SCI) leads to neuroinflammation and activates microglia, which are crucial contributors to neurological deficits. Betulinic acid (BA), a naturally occurring pentacyclic triterpenoid, has demonstrated effectiveness in treating inflammatory and neurological disorders. This study aims to explore the potential role and underlying mechanism of BA in modulating microglial activation and inflammation in the context of SCI. Using a mouse SCI model, we assessed motor recovery via Basso Mouse Scale (BMS) and neuronal survival via H&amp;E/Nissl staining. Western blotting, qPCR, immunofluorescence, and flow cytometry were employed to analyze microglial polarization, autophagy, and AMPK-HDAC5-KLF2 signaling in vivo and in LPS-stimulated BV2 cells. Our findings reveal that BA significantly enhances functional recovery and reduces neuronal apoptosis following SCI. Furthermore, BA facilitates the phenotypic transition of microglia from the M1 to M2 phenotype, thereby decreasing inflammatory factors in both the SCI model and LPS-stimulated BV2 cells. BA treatment restores the disrupted autophagy flux in microglia induced by SCI or LPS, which in turn mitigates M1 polarization and inflammation. Mechanistically, BA restores autophagy flux by activating the AMPK-HDAC5-KLF2 axis, thereby shifting microglia from pro-inflammatory M1 to anti-inflammatory M2 phenotype.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"158 ","pages":"Article 114889"},"PeriodicalIF":4.7000,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Betulinic acid enhances autopahgy to promote microglial M2 polarization and alleviate inflammation via AMPK-HDAC5-KLF2 signaling pathways in spinal cord injury\",\"authors\":\"Zili He ,&nbsp;Yitie Xu ,&nbsp;Yu Zhang ,&nbsp;Mengqi Jin ,&nbsp;Yinuo Sun ,&nbsp;Fangying Tang ,&nbsp;Chuangqi Qiu ,&nbsp;Abass Mashud Akinfemi Junior ,&nbsp;Yunhao Cai ,&nbsp;Xiaodan Xu ,&nbsp;Xianghang Chen ,&nbsp;Kongbin Chen ,&nbsp;Guangheng Xiang ,&nbsp;Jian Xiao ,&nbsp;Jian Wang ,&nbsp;Jing Wang ,&nbsp;Baoyi Chen\",\"doi\":\"10.1016/j.intimp.2025.114889\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Spinal cord injury (SCI) leads to neuroinflammation and activates microglia, which are crucial contributors to neurological deficits. Betulinic acid (BA), a naturally occurring pentacyclic triterpenoid, has demonstrated effectiveness in treating inflammatory and neurological disorders. This study aims to explore the potential role and underlying mechanism of BA in modulating microglial activation and inflammation in the context of SCI. Using a mouse SCI model, we assessed motor recovery via Basso Mouse Scale (BMS) and neuronal survival via H&amp;E/Nissl staining. Western blotting, qPCR, immunofluorescence, and flow cytometry were employed to analyze microglial polarization, autophagy, and AMPK-HDAC5-KLF2 signaling in vivo and in LPS-stimulated BV2 cells. Our findings reveal that BA significantly enhances functional recovery and reduces neuronal apoptosis following SCI. Furthermore, BA facilitates the phenotypic transition of microglia from the M1 to M2 phenotype, thereby decreasing inflammatory factors in both the SCI model and LPS-stimulated BV2 cells. BA treatment restores the disrupted autophagy flux in microglia induced by SCI or LPS, which in turn mitigates M1 polarization and inflammation. Mechanistically, BA restores autophagy flux by activating the AMPK-HDAC5-KLF2 axis, thereby shifting microglia from pro-inflammatory M1 to anti-inflammatory M2 phenotype.</div></div>\",\"PeriodicalId\":13859,\"journal\":{\"name\":\"International immunopharmacology\",\"volume\":\"158 \",\"pages\":\"Article 114889\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-05-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International immunopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1567576925008793\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1567576925008793","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

脊髓损伤导致神经炎症并激活小胶质细胞,而小胶质细胞是神经功能缺损的重要因素。白桦酸(BA)是一种天然存在的五环三萜,已被证明对治疗炎症和神经系统疾病有效。本研究旨在探讨BA在脊髓损伤中调节小胶质细胞激活和炎症的潜在作用及其机制。使用小鼠脊髓损伤模型,我们通过Basso小鼠量表(BMS)评估运动恢复,通过H&;E/Nissl染色评估神经元存活。采用Western blotting、qPCR、免疫荧光和流式细胞术分析体内和lps刺激的BV2细胞中的小胶质细胞极化、自噬和AMPK-HDAC5-KLF2信号。我们的研究结果表明,BA可显著促进脊髓损伤后的功能恢复,减少神经元凋亡。此外,BA促进了小胶质细胞从M1表型向M2表型的转变,从而降低了SCI模型和lps刺激的BV2细胞中的炎症因子。BA治疗可恢复脊髓损伤或LPS诱导的小胶质细胞自噬通量中断,从而减轻M1极化和炎症。从机制上讲,BA通过激活AMPK-HDAC5-KLF2轴恢复自噬通量,从而将小胶质细胞从促炎M1表型转变为抗炎M2表型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Betulinic acid enhances autopahgy to promote microglial M2 polarization and alleviate inflammation via AMPK-HDAC5-KLF2 signaling pathways in spinal cord injury
Spinal cord injury (SCI) leads to neuroinflammation and activates microglia, which are crucial contributors to neurological deficits. Betulinic acid (BA), a naturally occurring pentacyclic triterpenoid, has demonstrated effectiveness in treating inflammatory and neurological disorders. This study aims to explore the potential role and underlying mechanism of BA in modulating microglial activation and inflammation in the context of SCI. Using a mouse SCI model, we assessed motor recovery via Basso Mouse Scale (BMS) and neuronal survival via H&E/Nissl staining. Western blotting, qPCR, immunofluorescence, and flow cytometry were employed to analyze microglial polarization, autophagy, and AMPK-HDAC5-KLF2 signaling in vivo and in LPS-stimulated BV2 cells. Our findings reveal that BA significantly enhances functional recovery and reduces neuronal apoptosis following SCI. Furthermore, BA facilitates the phenotypic transition of microglia from the M1 to M2 phenotype, thereby decreasing inflammatory factors in both the SCI model and LPS-stimulated BV2 cells. BA treatment restores the disrupted autophagy flux in microglia induced by SCI or LPS, which in turn mitigates M1 polarization and inflammation. Mechanistically, BA restores autophagy flux by activating the AMPK-HDAC5-KLF2 axis, thereby shifting microglia from pro-inflammatory M1 to anti-inflammatory M2 phenotype.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信