Exosomal HMGB1 derived from hypoxia‐conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF‐1α pathway
Mesenchymal stem cells (MSCs) have been described to induce angiogenesis in various tissues and have been used for the development of novel cell‐based therapies. Increasing evidence suggests that MSCs execute their paracrine function via the secretion of exosomes, especially under hypoxic conditions...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-05-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.13142 |
| _version_ | 1827397655327670272 |
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| author | Wenling Gao Ronghan He Jianhua Ren Wenhui Zhang Kun Wang Lei Zhu Tangzhao Liang |
| author_facet | Wenling Gao Ronghan He Jianhua Ren Wenhui Zhang Kun Wang Lei Zhu Tangzhao Liang |
| author_sort | Wenling Gao |
| collection | DOAJ |
| description | Mesenchymal stem cells (MSCs) have been described to induce angiogenesis in various tissues and have been used for the development of novel cell‐based therapies. Increasing evidence suggests that MSCs execute their paracrine function via the secretion of exosomes, especially under hypoxic conditions. However, the mechanisms by which MSC‐derived exosomes secreted under hypoxia enhance angiogenesis still remain unclear. To study exosome physiology under hypoxic or normoxic conditions, we isolated exosomes from bone marrow mesenchymal stem cells (BMSCs). Furthermore, we detected the uptake of exosomes by human umbilical vein endothelial cells (HUVECs) by immunofluorescence staining. In addition, we determined the effects of exosomes on cell viability, migration and tube formation in HUVECs by Cell Counting Kit‐8, migration and tube formation assays, respectively. We examined the expression of key proteins related to exosome‐induced angiogenesis by BMSCs cultured under hypoxic conditions by western blot. Exosomes released by BMSCs cultured under hypoxic conditions enhanced cell proliferation, migration and angiogenesis of HUVECs. Hypoxia induced the expression of high mobility group box 1 protein (HMGB1) in BMSC‐derived exosomes, and silencing of HMGB1 abolished the angiogenic effect in HUVECs. Furthermore, exosomal HMGB1 activated the JNK signaling pathway and induced hypoxia‐inducible factor‐1α/vascular endothelial growth factor expression, consequently enhancing angiogenesis in HUVECs. Our data reveal that exosomal HMGB1 promotes angiogenesis via JNK/hypoxia‐inducible factor‐1α signaling. Therefore, BMSC exosomes derived under hypoxia may have potential for development of novel treatment strategies for angiogenesis‐related diseases. |
| first_indexed | 2024-03-08T19:12:43Z |
| format | Article |
| id | doaj.art-8a38bf94fac5444cb4a677b7806b2787 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-03-08T19:12:43Z |
| publishDate | 2021-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-8a38bf94fac5444cb4a677b7806b27872023-12-27T09:30:57ZengWileyFEBS Open Bio2211-54632021-05-011151364137310.1002/2211-5463.13142Exosomal HMGB1 derived from hypoxia‐conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF‐1α pathwayWenling Gao0Ronghan He1Jianhua Ren2Wenhui Zhang3Kun Wang4Lei Zhu5Tangzhao Liang6Department of Orthodontics Hospital of Stomatology Sun Yat‐sen University Guangzhou ChinaDepartment of Orthopaedic Surgery the Third Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Orthopaedic Surgery the Third Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Orthopaedic Surgery the Third Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Orthopaedic Surgery the Third Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Plastic and Reconstructive Surgery the Third Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Orthopaedic Surgery the Third Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaMesenchymal stem cells (MSCs) have been described to induce angiogenesis in various tissues and have been used for the development of novel cell‐based therapies. Increasing evidence suggests that MSCs execute their paracrine function via the secretion of exosomes, especially under hypoxic conditions. However, the mechanisms by which MSC‐derived exosomes secreted under hypoxia enhance angiogenesis still remain unclear. To study exosome physiology under hypoxic or normoxic conditions, we isolated exosomes from bone marrow mesenchymal stem cells (BMSCs). Furthermore, we detected the uptake of exosomes by human umbilical vein endothelial cells (HUVECs) by immunofluorescence staining. In addition, we determined the effects of exosomes on cell viability, migration and tube formation in HUVECs by Cell Counting Kit‐8, migration and tube formation assays, respectively. We examined the expression of key proteins related to exosome‐induced angiogenesis by BMSCs cultured under hypoxic conditions by western blot. Exosomes released by BMSCs cultured under hypoxic conditions enhanced cell proliferation, migration and angiogenesis of HUVECs. Hypoxia induced the expression of high mobility group box 1 protein (HMGB1) in BMSC‐derived exosomes, and silencing of HMGB1 abolished the angiogenic effect in HUVECs. Furthermore, exosomal HMGB1 activated the JNK signaling pathway and induced hypoxia‐inducible factor‐1α/vascular endothelial growth factor expression, consequently enhancing angiogenesis in HUVECs. Our data reveal that exosomal HMGB1 promotes angiogenesis via JNK/hypoxia‐inducible factor‐1α signaling. Therefore, BMSC exosomes derived under hypoxia may have potential for development of novel treatment strategies for angiogenesis‐related diseases.https://doi.org/10.1002/2211-5463.13142angiogenesisbone marrow mesenchymal stem cellsexosomeHMGB1hypoxia |
| spellingShingle | Wenling Gao Ronghan He Jianhua Ren Wenhui Zhang Kun Wang Lei Zhu Tangzhao Liang Exosomal HMGB1 derived from hypoxia‐conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF‐1α pathway FEBS Open Bio angiogenesis bone marrow mesenchymal stem cells exosome HMGB1 hypoxia |
| title | Exosomal HMGB1 derived from hypoxia‐conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF‐1α pathway |
| title_full | Exosomal HMGB1 derived from hypoxia‐conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF‐1α pathway |
| title_fullStr | Exosomal HMGB1 derived from hypoxia‐conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF‐1α pathway |
| title_full_unstemmed | Exosomal HMGB1 derived from hypoxia‐conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF‐1α pathway |
| title_short | Exosomal HMGB1 derived from hypoxia‐conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF‐1α pathway |
| title_sort | exosomal hmgb1 derived from hypoxia conditioned bone marrow mesenchymal stem cells increases angiogenesis via the jnk hif 1α pathway |
| topic | angiogenesis bone marrow mesenchymal stem cells exosome HMGB1 hypoxia |
| url | https://doi.org/10.1002/2211-5463.13142 |
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