MiR-146a-5p delivered by hucMSC extracellular vesicles modulates the inflammatory response to sulfur mustard-induced acute lung injury
Abstract Background Sulfur mustard (SM) is a highly toxic chemical warfare agent that has caused numerous casualties during wars and conflicts in the past century. Specific antidotes or therapeutic strategies are rare due to the complicated mechanism of toxicity, which still awaits elucidation. Clin...
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-023-03375-8 |
| _version_ | 1797811648208044032 |
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| author | Zhipeng Pei Jinfeng Cen Xinkang Zhang Chuchu Gong Mingxue Sun Wenqi Meng Guanchao Mao Jingjing Wan Bingyue Hu Xiaowen He Qingqiang Xu Hua Han Kai Xiao |
| author_facet | Zhipeng Pei Jinfeng Cen Xinkang Zhang Chuchu Gong Mingxue Sun Wenqi Meng Guanchao Mao Jingjing Wan Bingyue Hu Xiaowen He Qingqiang Xu Hua Han Kai Xiao |
| author_sort | Zhipeng Pei |
| collection | DOAJ |
| description | Abstract Background Sulfur mustard (SM) is a highly toxic chemical warfare agent that has caused numerous casualties during wars and conflicts in the past century. Specific antidotes or therapeutic strategies are rare due to the complicated mechanism of toxicity, which still awaits elucidation. Clinical data show that acute lung injury (ALI) is responsible for most mortality and morbidity after SM exposure. Extracellular vesicles are natural materials that participate in intercellular communication by delivering various substances and can be modified. In this study, we aim to show that extracellular vesicles derived from human umbilical cord mesenchymal stromal cells (hucMSC-EVs) could exert therapeutic effects on SM-induced ALI, and to explain the underlying mechanism of effects. Methods MiR-146a-5p contained in hucMSC-EVs may be involved in the process of hucMSC-EVs modulating the inflammatory response to SM-induced ALI. We utilized miR-146a-5p delivered by extracellular vesicles and further modified hucMSCs with a miR-146a-5p mimic or inhibitor to collect miR-146a-5p-overexpressing extracellular vesicles (miR-146a-5p+-EVs) or miR-146a-5p-underexpressing extracellular vesicles (miR-146a-5p−-EVs), respectively. Through in vivo and in vitro experiments, we investigated the mechanism. Results The effect of miR-146a-5p+-EVs on improving the inflammatory reaction tied to SM injury was better than that of hucMSC-EVs. We demonstrated that miR-146a-5p delivered by hucMSC-EVs targeted TRAF6 to negatively regulate inflammation in SM-induced ALI models in vitro and in vivo. Conclusion In summary, miR-146a-5p delivered by hucMSC-EVs targeted TRAF6, causing hucMSC-EVs to exert anti-inflammatory effects in SM-induced ALI; thus, hucMSC-EVs treatment may be a promising clinical therapeutic after SM exposure. Graphical Abstract |
| first_indexed | 2024-03-13T07:26:46Z |
| format | Article |
| id | doaj.art-c9e40444688f454dac32378014412f14 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-13T07:26:46Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-c9e40444688f454dac32378014412f142023-06-04T11:22:45ZengBMCStem Cell Research & Therapy1757-65122023-05-0114111710.1186/s13287-023-03375-8MiR-146a-5p delivered by hucMSC extracellular vesicles modulates the inflammatory response to sulfur mustard-induced acute lung injuryZhipeng Pei0Jinfeng Cen1Xinkang Zhang2Chuchu Gong3Mingxue Sun4Wenqi Meng5Guanchao Mao6Jingjing Wan7Bingyue Hu8Xiaowen He9Qingqiang Xu10Hua Han11Kai Xiao12Department of Protective Medicine Against Chemical Agents, Faculty of Naval Medicine, Naval Medical UniversityDepartment of Protective Medicine Against Chemical Agents, Faculty of Naval Medicine, Naval Medical UniversityDepartment of Protective Medicine Against Chemical Agents, Faculty of Naval Medicine, Naval Medical UniversityDepartment of Protective Medicine Against Chemical Agents, Faculty of Naval Medicine, Naval Medical UniversityDepartment of Protective Medicine Against Chemical Agents, Faculty of Naval Medicine, Naval Medical UniversityDepartment of Protective Medicine Against Chemical Agents, Faculty of Naval Medicine, Naval Medical UniversityDepartment of Protective Medicine Against Chemical Agents, Faculty of Naval Medicine, Naval Medical UniversityDepartment of Clinical Pharmacy, School of Pharmacy, Naval Medical UniversitySchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical UniversityOrigincell Technology Group Co., Ltd.Department of Protective Medicine Against Chemical Agents, Faculty of Naval Medicine, Naval Medical UniversitySchool of Medicine, Tongji UniversityDepartment of Protective Medicine Against Chemical Agents, Faculty of Naval Medicine, Naval Medical UniversityAbstract Background Sulfur mustard (SM) is a highly toxic chemical warfare agent that has caused numerous casualties during wars and conflicts in the past century. Specific antidotes or therapeutic strategies are rare due to the complicated mechanism of toxicity, which still awaits elucidation. Clinical data show that acute lung injury (ALI) is responsible for most mortality and morbidity after SM exposure. Extracellular vesicles are natural materials that participate in intercellular communication by delivering various substances and can be modified. In this study, we aim to show that extracellular vesicles derived from human umbilical cord mesenchymal stromal cells (hucMSC-EVs) could exert therapeutic effects on SM-induced ALI, and to explain the underlying mechanism of effects. Methods MiR-146a-5p contained in hucMSC-EVs may be involved in the process of hucMSC-EVs modulating the inflammatory response to SM-induced ALI. We utilized miR-146a-5p delivered by extracellular vesicles and further modified hucMSCs with a miR-146a-5p mimic or inhibitor to collect miR-146a-5p-overexpressing extracellular vesicles (miR-146a-5p+-EVs) or miR-146a-5p-underexpressing extracellular vesicles (miR-146a-5p−-EVs), respectively. Through in vivo and in vitro experiments, we investigated the mechanism. Results The effect of miR-146a-5p+-EVs on improving the inflammatory reaction tied to SM injury was better than that of hucMSC-EVs. We demonstrated that miR-146a-5p delivered by hucMSC-EVs targeted TRAF6 to negatively regulate inflammation in SM-induced ALI models in vitro and in vivo. Conclusion In summary, miR-146a-5p delivered by hucMSC-EVs targeted TRAF6, causing hucMSC-EVs to exert anti-inflammatory effects in SM-induced ALI; thus, hucMSC-EVs treatment may be a promising clinical therapeutic after SM exposure. Graphical Abstracthttps://doi.org/10.1186/s13287-023-03375-8hucMSC-EVsSulfur mustardInflammationmiR-146a-5pTRAF6 |
| spellingShingle | Zhipeng Pei Jinfeng Cen Xinkang Zhang Chuchu Gong Mingxue Sun Wenqi Meng Guanchao Mao Jingjing Wan Bingyue Hu Xiaowen He Qingqiang Xu Hua Han Kai Xiao MiR-146a-5p delivered by hucMSC extracellular vesicles modulates the inflammatory response to sulfur mustard-induced acute lung injury Stem Cell Research & Therapy hucMSC-EVs Sulfur mustard Inflammation miR-146a-5p TRAF6 |
| title | MiR-146a-5p delivered by hucMSC extracellular vesicles modulates the inflammatory response to sulfur mustard-induced acute lung injury |
| title_full | MiR-146a-5p delivered by hucMSC extracellular vesicles modulates the inflammatory response to sulfur mustard-induced acute lung injury |
| title_fullStr | MiR-146a-5p delivered by hucMSC extracellular vesicles modulates the inflammatory response to sulfur mustard-induced acute lung injury |
| title_full_unstemmed | MiR-146a-5p delivered by hucMSC extracellular vesicles modulates the inflammatory response to sulfur mustard-induced acute lung injury |
| title_short | MiR-146a-5p delivered by hucMSC extracellular vesicles modulates the inflammatory response to sulfur mustard-induced acute lung injury |
| title_sort | mir 146a 5p delivered by hucmsc extracellular vesicles modulates the inflammatory response to sulfur mustard induced acute lung injury |
| topic | hucMSC-EVs Sulfur mustard Inflammation miR-146a-5p TRAF6 |
| url | https://doi.org/10.1186/s13287-023-03375-8 |
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