Serum Exosomes miR-122-5P Induces Hepatic and Renal Injury in Septic Rats by Regulating TAK1/SIRT1 Pathway
Jiaqi Wang, Yujing Jiang, Yamin Yuan, Xin Ma, Tongqin Li, YaTing Lv, Jing Zhang, Liao Chen, Jinquan Zhou, Yanfei Meng, Bei Zhang, Xiaorong Dong, Li Ma Department of Critical Care Medicine, Lanzhou University Second Hospital, Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of Chin...
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Dove Medical Press
2025-01-01
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| Series: | Infection and Drug Resistance |
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| Online Access: | https://www.dovepress.com/serum-exosomes-mir-122-5p-induces-hepatic-and-renal-injury-in-septic-r-peer-reviewed-fulltext-article-IDR |
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| author | Wang J Jiang Y Yuan Y Ma X Li T Lv Y Zhang J Chen L Zhou J Meng Y Zhang B Dong X Ma L |
| author_facet | Wang J Jiang Y Yuan Y Ma X Li T Lv Y Zhang J Chen L Zhou J Meng Y Zhang B Dong X Ma L |
| author_sort | Wang J |
| collection | DOAJ |
| description | Jiaqi Wang, Yujing Jiang, Yamin Yuan, Xin Ma, Tongqin Li, YaTing Lv, Jing Zhang, Liao Chen, Jinquan Zhou, Yanfei Meng, Bei Zhang, Xiaorong Dong, Li Ma Department of Critical Care Medicine, Lanzhou University Second Hospital, Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of ChinaCorrespondence: Li Ma, Email ery_mali@lzu.edu.cnAim: Sepsis is a potentially fatal condition characterized by organ failure resulting from an abnormal host response to infection, often leading to liver and kidney damage. Timely recognition and intervention of these dysfunctions have the potential to significantly reduce sepsis mortality rates. Recent studies have emphasized the critical role of serum exosomes and their miRNA content in mediating sepsis-induced organ dysfunction. The objective of this study is to elucidate the mechanism underlying the impact of miR-122-5p on sepsis-associated liver and kidney injury using inhibitors for miR-122-5p as well as GW4869, an inhibitor targeting exosome release.Materials and Methods: Exosomes were isolated from serum samples of septic rats, sepsis patients, and control groups, while liver and kidney tissues were collected for subsequent analysis. The levels of miR-122-5p, inflammation indices, and organ damage were assessed using PCR, ELISA, and pathological identification techniques. Immunohistochemistry and Western blotting methods were employed to investigate the activation of inflammatory pathways. Furthermore, big data analysis was utilized to screen potential targets of miR-122-5p in vivo.Key Findings: Serum exosomal levels of miR-122-5p were significantly elevated in septic patients as well as in LPS-induced septic rats. Inhibition of miR-122-5p reduced serum pro-inflammatory factors and ameliorated liver and kidney damage in septic rats. Mechanistically, miR-122-5p upregulated TAK1, downregulated SIRT1, and facilitated NF-κB activation.Conclusion: Serum exosomal miR-122-5p promotes inflammation and induces liver/kidney injury in LPS-induced septic rats by modulating the TAK1/SIRT1/NF-κB pathway, highlighting potential therapeutic targets for sepsis management.Keywords: sepsis, exosome, miR-122-5p, NF-κB signaling pathway, sepsis-related liver and kidney injury |
| format | Article |
| id | doaj-art-275c5c4f949e45b78b72021b7e0961ae |
| institution | Kabale University |
| issn | 1178-6973 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Infection and Drug Resistance |
| spelling | doaj-art-275c5c4f949e45b78b72021b7e0961ae2025-01-09T16:58:35ZengDove Medical PressInfection and Drug Resistance1178-69732025-01-01Volume 1818519799111Serum Exosomes miR-122-5P Induces Hepatic and Renal Injury in Septic Rats by Regulating TAK1/SIRT1 PathwayWang JJiang YYuan YMa XLi TLv YZhang JChen LZhou JMeng YZhang BDong XMa LJiaqi Wang, Yujing Jiang, Yamin Yuan, Xin Ma, Tongqin Li, YaTing Lv, Jing Zhang, Liao Chen, Jinquan Zhou, Yanfei Meng, Bei Zhang, Xiaorong Dong, Li Ma Department of Critical Care Medicine, Lanzhou University Second Hospital, Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of ChinaCorrespondence: Li Ma, Email ery_mali@lzu.edu.cnAim: Sepsis is a potentially fatal condition characterized by organ failure resulting from an abnormal host response to infection, often leading to liver and kidney damage. Timely recognition and intervention of these dysfunctions have the potential to significantly reduce sepsis mortality rates. Recent studies have emphasized the critical role of serum exosomes and their miRNA content in mediating sepsis-induced organ dysfunction. The objective of this study is to elucidate the mechanism underlying the impact of miR-122-5p on sepsis-associated liver and kidney injury using inhibitors for miR-122-5p as well as GW4869, an inhibitor targeting exosome release.Materials and Methods: Exosomes were isolated from serum samples of septic rats, sepsis patients, and control groups, while liver and kidney tissues were collected for subsequent analysis. The levels of miR-122-5p, inflammation indices, and organ damage were assessed using PCR, ELISA, and pathological identification techniques. Immunohistochemistry and Western blotting methods were employed to investigate the activation of inflammatory pathways. Furthermore, big data analysis was utilized to screen potential targets of miR-122-5p in vivo.Key Findings: Serum exosomal levels of miR-122-5p were significantly elevated in septic patients as well as in LPS-induced septic rats. Inhibition of miR-122-5p reduced serum pro-inflammatory factors and ameliorated liver and kidney damage in septic rats. Mechanistically, miR-122-5p upregulated TAK1, downregulated SIRT1, and facilitated NF-κB activation.Conclusion: Serum exosomal miR-122-5p promotes inflammation and induces liver/kidney injury in LPS-induced septic rats by modulating the TAK1/SIRT1/NF-κB pathway, highlighting potential therapeutic targets for sepsis management.Keywords: sepsis, exosome, miR-122-5p, NF-κB signaling pathway, sepsis-related liver and kidney injuryhttps://www.dovepress.com/serum-exosomes-mir-122-5p-induces-hepatic-and-renal-injury-in-septic-r-peer-reviewed-fulltext-article-IDRsepsisexosomemir-122-5pnf-κb signaling pathwaysepsis-related liver and kidney injury |
| spellingShingle | Wang J Jiang Y Yuan Y Ma X Li T Lv Y Zhang J Chen L Zhou J Meng Y Zhang B Dong X Ma L Serum Exosomes miR-122-5P Induces Hepatic and Renal Injury in Septic Rats by Regulating TAK1/SIRT1 Pathway Infection and Drug Resistance sepsis exosome mir-122-5p nf-κb signaling pathway sepsis-related liver and kidney injury |
| title | Serum Exosomes miR-122-5P Induces Hepatic and Renal Injury in Septic Rats by Regulating TAK1/SIRT1 Pathway |
| title_full | Serum Exosomes miR-122-5P Induces Hepatic and Renal Injury in Septic Rats by Regulating TAK1/SIRT1 Pathway |
| title_fullStr | Serum Exosomes miR-122-5P Induces Hepatic and Renal Injury in Septic Rats by Regulating TAK1/SIRT1 Pathway |
| title_full_unstemmed | Serum Exosomes miR-122-5P Induces Hepatic and Renal Injury in Septic Rats by Regulating TAK1/SIRT1 Pathway |
| title_short | Serum Exosomes miR-122-5P Induces Hepatic and Renal Injury in Septic Rats by Regulating TAK1/SIRT1 Pathway |
| title_sort | serum exosomes mir 122 5p induces hepatic and renal injury in septic rats by regulating tak1 sirt1 pathway |
| topic | sepsis exosome mir-122-5p nf-κb signaling pathway sepsis-related liver and kidney injury |
| url | https://www.dovepress.com/serum-exosomes-mir-122-5p-induces-hepatic-and-renal-injury-in-septic-r-peer-reviewed-fulltext-article-IDR |
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