Heparan sulfate proteoglycan-mediated internalization of extracellular vesicles ameliorates liver fibrosis by targeting hepatic stellate cells
Accumulating evidence shows that stem cell-derived extracellular vesicles (EVs) have shown great promise for tissue regeneration and are considered an alternative to cell-based therapy. However, the mechanisms by which EVs induce tissue repair have not been well demonstrated. Previous work indicates...
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Elsevier
2022-12-01
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| Series: | Extracellular Vesicle |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2773041722000130 |
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| author | Rongrong Li Chen Wang Manqian Zhou Yue Liu Shang Chen Zihan Chai Haoyan Huang Kaiyue Zhang Zhibo Han Guoqiang Hua Nadia Benkirane-Jessel Zhong-Chao Han Zongjin Li |
| author_facet | Rongrong Li Chen Wang Manqian Zhou Yue Liu Shang Chen Zihan Chai Haoyan Huang Kaiyue Zhang Zhibo Han Guoqiang Hua Nadia Benkirane-Jessel Zhong-Chao Han Zongjin Li |
| author_sort | Rongrong Li |
| collection | DOAJ |
| description | Accumulating evidence shows that stem cell-derived extracellular vesicles (EVs) have shown great promise for tissue regeneration and are considered an alternative to cell-based therapy. However, the mechanisms by which EVs induce tissue repair have not been well demonstrated. Previous work indicates that activation of hepatic stellate cells (HSCs) may contribute to the progression of liver fibrosis. Here, we investigate the therapeutic potential of EVs derived from human placental mesenchymal stem cells (hP-MSCs) for the treatment of carbon tetrachloride (CCl4)-induced liver injury. Our data revealed that EVs derived from hP-MSCs effectively ameliorate liver injury by attenuating inflammation and fibrosis. Further data revealed that heparan sulfate proteoglycans (HSPGs) on the surface of HSCs mediate the internalization of EVs. Furthermore, EVs could inhibit the epithelial–mesenchymal transition (EMT) process in HSCs through the downregulated TGF-β/Smad pathway, which was mediated by miR-744-5p in EVs. Meanwhile, glycosaminoglycans on the surface of EVs play a crucial anti-inflammatory role. In conclusion, our results provide evidence that hP-MSC-derived EVs promote the recovery of liver injury by targeting HSPGs on HSCs and inhibiting liver inflammation through glycosaminoglycans from EVs. These findings may provide a novel theoretical basis for the treatment of liver fibrosis based on EVs. |
| format | Article |
| id | doaj-art-e8c92151beb4473085c837ac8cf3c0cd |
| institution | OA Journals |
| issn | 2773-0417 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Extracellular Vesicle |
| spelling | doaj-art-e8c92151beb4473085c837ac8cf3c0cd2025-08-20T02:02:58ZengElsevierExtracellular Vesicle2773-04172022-12-01110001810.1016/j.vesic.2022.100018Heparan sulfate proteoglycan-mediated internalization of extracellular vesicles ameliorates liver fibrosis by targeting hepatic stellate cellsRongrong Li0Chen Wang1Manqian Zhou2Yue Liu3Shang Chen4Zihan Chai5Haoyan Huang6Kaiyue Zhang7Zhibo Han8Guoqiang Hua9Nadia Benkirane-Jessel10Zhong-Chao Han11Zongjin Li12Nankai University School of Medicine, Tianjin 300071, China; Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Hospital of Obstetrics and Gynecology, Tianjin 300052, China; The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, College of Life Sciences, Tianjin 300071, ChinaNankai University School of Medicine, Tianjin 300071, China; Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Hospital of Obstetrics and Gynecology, Tianjin 300052, China; The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, College of Life Sciences, Tianjin 300071, ChinaDepartment of Radiation Oncology, Tianjin Union Medical Center, Nankai University, Tianjin 300120, ChinaNankai University School of Medicine, Tianjin 300071, ChinaNankai University School of Medicine, Tianjin 300071, ChinaNankai University School of Medicine, Tianjin 300071, ChinaNankai University School of Medicine, Tianjin 300071, ChinaNankai University School of Medicine, Tianjin 300071, ChinaJiangxi Engineering Research Center for Stem Cells, Shangrao 334109, Jiangxi, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceuticals, National Engineering Research Center of Cell Products, AmCellGene Co., Ltd., Tianjin 300457, China; Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co., Beijing 100176, ChinaINSERM (French Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France; Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, FranceINSERM (French Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France; Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, FranceJiangxi Engineering Research Center for Stem Cells, Shangrao 334109, Jiangxi, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceuticals, National Engineering Research Center of Cell Products, AmCellGene Co., Ltd., Tianjin 300457, China; Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co., Beijing 100176, ChinaNankai University School of Medicine, Tianjin 300071, China; Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Hospital of Obstetrics and Gynecology, Tianjin 300052, China; The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, College of Life Sciences, Tianjin 300071, China; State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing 100039, China; Correspondence to: Nankai University, 94 Weijin Road, Tianjin, China.Accumulating evidence shows that stem cell-derived extracellular vesicles (EVs) have shown great promise for tissue regeneration and are considered an alternative to cell-based therapy. However, the mechanisms by which EVs induce tissue repair have not been well demonstrated. Previous work indicates that activation of hepatic stellate cells (HSCs) may contribute to the progression of liver fibrosis. Here, we investigate the therapeutic potential of EVs derived from human placental mesenchymal stem cells (hP-MSCs) for the treatment of carbon tetrachloride (CCl4)-induced liver injury. Our data revealed that EVs derived from hP-MSCs effectively ameliorate liver injury by attenuating inflammation and fibrosis. Further data revealed that heparan sulfate proteoglycans (HSPGs) on the surface of HSCs mediate the internalization of EVs. Furthermore, EVs could inhibit the epithelial–mesenchymal transition (EMT) process in HSCs through the downregulated TGF-β/Smad pathway, which was mediated by miR-744-5p in EVs. Meanwhile, glycosaminoglycans on the surface of EVs play a crucial anti-inflammatory role. In conclusion, our results provide evidence that hP-MSC-derived EVs promote the recovery of liver injury by targeting HSPGs on HSCs and inhibiting liver inflammation through glycosaminoglycans from EVs. These findings may provide a novel theoretical basis for the treatment of liver fibrosis based on EVs.http://www.sciencedirect.com/science/article/pii/S2773041722000130Extracellular vesiclesLiver fibrosisHepatic stellate cellHeparan sulfate proteoglycansGlycosaminoglycans |
| spellingShingle | Rongrong Li Chen Wang Manqian Zhou Yue Liu Shang Chen Zihan Chai Haoyan Huang Kaiyue Zhang Zhibo Han Guoqiang Hua Nadia Benkirane-Jessel Zhong-Chao Han Zongjin Li Heparan sulfate proteoglycan-mediated internalization of extracellular vesicles ameliorates liver fibrosis by targeting hepatic stellate cells Extracellular Vesicle Extracellular vesicles Liver fibrosis Hepatic stellate cell Heparan sulfate proteoglycans Glycosaminoglycans |
| title | Heparan sulfate proteoglycan-mediated internalization of extracellular vesicles ameliorates liver fibrosis by targeting hepatic stellate cells |
| title_full | Heparan sulfate proteoglycan-mediated internalization of extracellular vesicles ameliorates liver fibrosis by targeting hepatic stellate cells |
| title_fullStr | Heparan sulfate proteoglycan-mediated internalization of extracellular vesicles ameliorates liver fibrosis by targeting hepatic stellate cells |
| title_full_unstemmed | Heparan sulfate proteoglycan-mediated internalization of extracellular vesicles ameliorates liver fibrosis by targeting hepatic stellate cells |
| title_short | Heparan sulfate proteoglycan-mediated internalization of extracellular vesicles ameliorates liver fibrosis by targeting hepatic stellate cells |
| title_sort | heparan sulfate proteoglycan mediated internalization of extracellular vesicles ameliorates liver fibrosis by targeting hepatic stellate cells |
| topic | Extracellular vesicles Liver fibrosis Hepatic stellate cell Heparan sulfate proteoglycans Glycosaminoglycans |
| url | http://www.sciencedirect.com/science/article/pii/S2773041722000130 |
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