Exosomal HMGB1 derived from hypoxia-conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF-1α pathway.
Exosomal HMGB1 derived from hypoxia-conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF-1α pathway.
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源自缺氧条件的骨髓间充质干细胞的外泌体 HMGB1 通过 JNK/HIF-1α 途径增加血管生成
DOI：
10.1002/2211-5463.13142
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发表时间：
2021-05
期刊：
影响因子：
2.6
通讯作者：
Liang T
中科院分区：
文献类型：
--
作者：
Gao W;He R;Ren J;Zhang W;Wang K;Zhu L;Liang T
间充质干细胞（MSC）已被描述为在各种组织中诱导血管生成，并已用于开发新的基于细胞的疗法。越来越多的证据表明，MSC通过分泌外泌体来执行其旁分泌功能，特别是在缺氧条件下。然而，在低氧条件下分泌的MSC来源的外泌体增强血管生成的机制仍然不清楚。为了研究外泌体在缺氧或常氧条件下的生理学，我们从骨髓间充质干细胞（BMSCs）中分离外泌体。此外，我们通过免疫荧光染色检测了人脐静脉内皮细胞（HUVECs）对exosomes的摄取。此外，我们分别通过细胞计数试剂盒-8、迁移和管形成试验确定了外泌体对HUVEC中细胞活力、迁移和管形成的影响。我们通过western blot检测了在缺氧条件下培养的BMSCs中与外泌体诱导的血管生成相关的关键蛋白的表达。低氧条件下培养的BMSCs释放的Exosomes促进HUVECs的增殖、迁移和血管生成。缺氧诱导BMSC来源的外泌体中高迁移率族蛋白1（HMGB 1）的表达，并且HMGB 1的沉默消除了HUVECs中的血管生成作用。此外，外泌体HMGB 1激活JNK信号通路并诱导缺氧诱导因子-1 α/血管内皮生长因子表达，从而增强HUVECs中的血管生成。我们的数据表明，外泌体HMGB 1通过JNK/缺氧诱导因子-1 α信号转导促进血管生成。因此，在缺氧条件下衍生的BMSC外泌体可能具有开发血管生成相关疾病的新治疗策略的潜力。为了研究在低氧或常氧条件下来自骨髓间充质干细胞的外泌体生理学，我们确定了外泌体对人脐静脉内皮细胞中的细胞活力、迁移和管形成的影响。我们的数据表明，外泌体高迁移率族蛋白1蛋白促进缺氧条件下的血管生成。在低氧条件下获得的骨髓间充质干细胞外泌体可能具有开发血管生成相关疾病的新治疗策略的潜力。
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. To study exosome physiology under hypoxic or normoxic conditions from bone marrow mesenchymal stem cells, we determined the effects of exosomes on cell viability, migration and tube formation in human umbilical vein endothelial cells. Our data reveal that exosomal high mobility group box 1 protein promotes angiogenesis under hypoxic conditions. Bone marrow mesenchymal stem cell exosomes obtained under hypoxic conditions may have potential for development of novel treatment strategies for angiogenesis‐related diseases.
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DOI：
10.1002/iid3.370
发表时间：
2021-03
期刊：
Immunity, inflammation and disease
影响因子：
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