Human umbilical cord mesenchymal stem cells derived exosome shuttling mir-129-5p attenuates inflammatory bowel disease by inhibiting ferroptosis
Abstract Background Ferroptosis, a unique form of non-apoptotic cell death, is dependent on iron and lipoperoxidation, and has been shown to be associated with the pathogenesis of inflammatory bowel disease (IBD). Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) are involved i...
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-023-01951-x |
| _version_ | 1827922783412158464 |
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| author | Zhiping Wei Sanhua Hang Dickson Kofi Wiredu Ocansey Zhaoyang Zhang Bo Wang Xu Zhang Fei Mao |
| author_facet | Zhiping Wei Sanhua Hang Dickson Kofi Wiredu Ocansey Zhaoyang Zhang Bo Wang Xu Zhang Fei Mao |
| author_sort | Zhiping Wei |
| collection | DOAJ |
| description | Abstract Background Ferroptosis, a unique form of non-apoptotic cell death, is dependent on iron and lipoperoxidation, and has been shown to be associated with the pathogenesis of inflammatory bowel disease (IBD). Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) are involved in cell survival, immune conditioning, and damage repair. However, the relationship between hucMSC-Ex, IBD, and ferroptosis is unknown. This paper explores the role of hucMSC-Ex in the repair of IBD through the regulation of the ferroptosis signaling pathway. Results In this study, we used small RNA sequencing to find that miR-129-5p was highly expressed in hucMSC-Ex, and by predicting its targeting to ACSL4, we verified the effect of miR-129-5p on mice IBD in vitro and human colonic epithelial cells (HCoEpiC) in vivo. We found that miR-129-5p reduces ferroptosis in intestinal epithelial cells by targeting ACSL4 to repair IBD, which provides new strategies for the prevention and treatment of IBD. Conclusion In conclusion, our results demonstrate that hucMSC-Ex relieves IBD by targeting ACSL4 with miR-129-5p to inhibit lipid peroxidation (LPO) and ferroptosis, reducing intestinal inflammation and repairing damages. Graphic abstract Mechanism of hucMSC-Ex inhibiting ferroptosis in intestinal epithelial cells. System Xc− mediates the transport of extracellular cystine into the cell, which gets reduced to cysteine to participate in GSH-mediated metabolism. GPX4 strongly inhibits ferroptosis by helping scavenge reactive oxygen species. The depletion of GSH correlates with decreased GPX4, and the imbalance of the antioxidant system leads to the formation of toxic phospholipid hydroperoxide, which promotes the occurrence of ferroptosis with the participation of irons. HucMSC-Ex has the ability to relieve GSH and GPX4 depletion and repair the intracellular antioxidant system. Ferric ions enter the cytosol through DMT1 and participate in lipid peroxidation. HucMSC-Ex can reduce the expression of DMT1 and alleviate this process. HucMSC-Ex-derived miR-129-5p targets ACSL4 and reduces the expression of ACSL4, an enzyme that mediates the conversion of PUFAs into phospholipids in intestinal epithelial cells, and is a positive regulator of lipid peroxidation. Abbreviations: GSH, glutathione; GPX4, glutathione peroxidase 4; GSSG, oxidized glutathione; DMT1, divalent metal transporter 1; ACSL4, acyl-CoA synthetase long-chain family member 4; PUFAs, polyunsaturated fatty acids; ALOXs, lipoxygenases; CoA, coenzyme A; PL, phospholipid; PLOOH, hydroperoxides, LOH, phospholipid alcohols; LPO, lipid peroxidation. |
| first_indexed | 2024-03-13T04:47:41Z |
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| id | doaj.art-a4063b2a78c041d5a53b436c6c1e5633 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-13T04:47:41Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-a4063b2a78c041d5a53b436c6c1e56332023-06-18T11:24:05ZengBMCJournal of Nanobiotechnology1477-31552023-06-0121111910.1186/s12951-023-01951-xHuman umbilical cord mesenchymal stem cells derived exosome shuttling mir-129-5p attenuates inflammatory bowel disease by inhibiting ferroptosisZhiping Wei0Sanhua Hang1Dickson Kofi Wiredu Ocansey2Zhaoyang Zhang3Bo Wang4Xu Zhang5Fei Mao6Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu UniversityThe People’s Hospital of Danyang, Affiliated Danyang Hospital of Nantong UniversityKey Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu UniversityClinical Lab, Taicang Hospital of Traditional Chinese MedicineKey Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu UniversityKey Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu UniversityKey Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu UniversityAbstract Background Ferroptosis, a unique form of non-apoptotic cell death, is dependent on iron and lipoperoxidation, and has been shown to be associated with the pathogenesis of inflammatory bowel disease (IBD). Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) are involved in cell survival, immune conditioning, and damage repair. However, the relationship between hucMSC-Ex, IBD, and ferroptosis is unknown. This paper explores the role of hucMSC-Ex in the repair of IBD through the regulation of the ferroptosis signaling pathway. Results In this study, we used small RNA sequencing to find that miR-129-5p was highly expressed in hucMSC-Ex, and by predicting its targeting to ACSL4, we verified the effect of miR-129-5p on mice IBD in vitro and human colonic epithelial cells (HCoEpiC) in vivo. We found that miR-129-5p reduces ferroptosis in intestinal epithelial cells by targeting ACSL4 to repair IBD, which provides new strategies for the prevention and treatment of IBD. Conclusion In conclusion, our results demonstrate that hucMSC-Ex relieves IBD by targeting ACSL4 with miR-129-5p to inhibit lipid peroxidation (LPO) and ferroptosis, reducing intestinal inflammation and repairing damages. Graphic abstract Mechanism of hucMSC-Ex inhibiting ferroptosis in intestinal epithelial cells. System Xc− mediates the transport of extracellular cystine into the cell, which gets reduced to cysteine to participate in GSH-mediated metabolism. GPX4 strongly inhibits ferroptosis by helping scavenge reactive oxygen species. The depletion of GSH correlates with decreased GPX4, and the imbalance of the antioxidant system leads to the formation of toxic phospholipid hydroperoxide, which promotes the occurrence of ferroptosis with the participation of irons. HucMSC-Ex has the ability to relieve GSH and GPX4 depletion and repair the intracellular antioxidant system. Ferric ions enter the cytosol through DMT1 and participate in lipid peroxidation. HucMSC-Ex can reduce the expression of DMT1 and alleviate this process. HucMSC-Ex-derived miR-129-5p targets ACSL4 and reduces the expression of ACSL4, an enzyme that mediates the conversion of PUFAs into phospholipids in intestinal epithelial cells, and is a positive regulator of lipid peroxidation. Abbreviations: GSH, glutathione; GPX4, glutathione peroxidase 4; GSSG, oxidized glutathione; DMT1, divalent metal transporter 1; ACSL4, acyl-CoA synthetase long-chain family member 4; PUFAs, polyunsaturated fatty acids; ALOXs, lipoxygenases; CoA, coenzyme A; PL, phospholipid; PLOOH, hydroperoxides, LOH, phospholipid alcohols; LPO, lipid peroxidation.https://doi.org/10.1186/s12951-023-01951-xMesenchymal stem cell-derived exosomesFerroptosismiR-129-5pInflammatory bowel diseaseACSL4Lipid peroxidation |
| spellingShingle | Zhiping Wei Sanhua Hang Dickson Kofi Wiredu Ocansey Zhaoyang Zhang Bo Wang Xu Zhang Fei Mao Human umbilical cord mesenchymal stem cells derived exosome shuttling mir-129-5p attenuates inflammatory bowel disease by inhibiting ferroptosis Journal of Nanobiotechnology Mesenchymal stem cell-derived exosomes Ferroptosis miR-129-5p Inflammatory bowel disease ACSL4 Lipid peroxidation |
| title | Human umbilical cord mesenchymal stem cells derived exosome shuttling mir-129-5p attenuates inflammatory bowel disease by inhibiting ferroptosis |
| title_full | Human umbilical cord mesenchymal stem cells derived exosome shuttling mir-129-5p attenuates inflammatory bowel disease by inhibiting ferroptosis |
| title_fullStr | Human umbilical cord mesenchymal stem cells derived exosome shuttling mir-129-5p attenuates inflammatory bowel disease by inhibiting ferroptosis |
| title_full_unstemmed | Human umbilical cord mesenchymal stem cells derived exosome shuttling mir-129-5p attenuates inflammatory bowel disease by inhibiting ferroptosis |
| title_short | Human umbilical cord mesenchymal stem cells derived exosome shuttling mir-129-5p attenuates inflammatory bowel disease by inhibiting ferroptosis |
| title_sort | human umbilical cord mesenchymal stem cells derived exosome shuttling mir 129 5p attenuates inflammatory bowel disease by inhibiting ferroptosis |
| topic | Mesenchymal stem cell-derived exosomes Ferroptosis miR-129-5p Inflammatory bowel disease ACSL4 Lipid peroxidation |
| url | https://doi.org/10.1186/s12951-023-01951-x |
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