Exosomes Derived from Human Endothelial Progenitor Cells Accelerate Cutaneous Wound Healing by Promoting Angiogenesis Through Erk1/2 Signaling.
Exosomes Derived from Human Endothelial Progenitor Cells Accelerate Cutaneous Wound Healing by Promoting Angiogenesis Through Erk1/2 Signaling.
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源自人内皮祖细胞的外泌体通过 Erk1/2 信号传导促进血管生成，加速皮肤伤口愈合
DOI：
10.7150/ijbs.15514
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发表时间：
2016
影响因子：
9.2
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Zhang J;Chen C;Hu B;Niu X;Liu X;Zhang G;Zhang C;Li Q;Wang Y
慢性皮肤伤口是糖尿病最常见和致残的并发症之一。内皮祖细胞（EPC）是内皮细胞的前体，可以通过促进新血管形成来增强糖尿病伤口的修复。最近的研究表明，移植细胞主要通过旁分泌机制发挥治疗作用，外泌体是重要的旁分泌因子，可直接用作再生医学的治疗剂。然而，外泌体在糖尿病伤口修复中的应用鲜有报道。在这项研究中，我们证明，源自人脐带血来源的 EPC（EPC-Exos）的外泌体在链脲佐菌素诱导的糖尿病大鼠中具有强大的促血管生成和伤口愈合作用。通过一系列体外功能测定，我们发现EPC-Exos可以整合到内皮细胞中，并显着增强内皮细胞的增殖、迁移和血管生成小管的形成。此外，微阵列分析表明，外泌体处理显着改变了参与 Erk1/2 信号通路的一类基因的表达。功能研究进一步证实，该信号传导过程是外泌体诱导内皮细胞血管生成反应过程中的关键介质。因此，EPC-Exos能够通过激活Erk1/2信号来刺激内皮细胞的血管生成活性，最终促进皮肤伤口的修复和再生。
Chronic skin wounds represent one of the most common and disabling complications of diabetes. Endothelial progenitor cells (EPCs) are precursors of endothelial cells and can enhance diabetic wound repair by facilitating neovascularization. Recent studies indicate that the transplanted cells exert therapeutic effects primarily via a paracrine mechanism and exosomes are an important paracrine factor that can be directly used as therapeutic agents for regenerative medicine. However, application of exosomes in diabetic wound repair has been rarely reported. In this study, we demonstrated that the exosomes derived from human umbilical cord blood-derived EPCs (EPC-Exos) possessed robust pro-angiogenic and wound healing effects in streptozotocin-induced diabetic rats. By using a series of in vitro functional assays, we found that EPC-Exos could be incorporated into endothelial cells and significantly enhance endothelial cells' proliferation, migration, and angiogenic tubule formation. Moreover, microarray analyses indicated that exosomes treatment markedly altered the expression of a class of genes involved in Erk1/2 signaling pathway. It was further confirmed with functional study that this signaling process was the critical mediator during the exosomes-induced angiogenic responses of endothelial cells. Therefore, EPC-Exos are able to stimulate angiogenic activities of endothelial cells by activating Erk1/2 signaling, which finally facilitates cutaneous wound repair and regeneration.
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影响因子：
21.3
作者：
Hergenreider, Eduard;Heydt, Susanne;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
影响因子：
--
作者：
Kota SK;Meher LK;Jammula S;Kota SK;Krishna SV;Modi KD
通讯作者：
Modi KD
影响因子：
4.6
作者：
Cheng, Biao;Liu, Hong-Wei;Sheng, Zhi-Yong
通讯作者：
Sheng, Zhi-Yong
DOI：
10.1186/s13054-015-1162-8
发表时间：
2015-12-18
期刊：
Critical care (London, England)
影响因子：
--
作者：
Goodwin AJ;Guo C;Cook JA;Wolf B;Halushka PV;Fan H
通讯作者：
Fan H
影响因子：
2.2
作者：
Critser PJ;Yoder MC
通讯作者：
Yoder MC