Department of Surgery, University of California-San Diego, La Jolla, California, USA.
Department of Plastic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China; and.
FASEB J. 2019 May;33(5):6129-6139. doi: 10.1096/fj.201802388R. Epub 2019 Feb 4.
Healthy repair of cutaneous injury is a coordinated response of inflammatory cells, secreted factors, and biologically active extracellular vesicles (EVs). Although constitutive release of EVs into biologic fluids is a hallmark of cultured cells and tumors, their payload and biologic activity appears to be tightly regulated. We show that Tre-2/Bub2/Cdc16 (TBC1) domain family member 3 (TBC1D3) drives the release of an EV population that causes a decrease in phosphorylation of the transcription factor signal transducer and activator of transcription 3 in naive recipient cells. To explore the biologic activity of EVs , we used a mouse model of sterile subcutaneous inflammation to determine the payload and biologic activity of EVs released into the microenvironment by committed myeloid lineages and stroma. Expression of TBC1D3 in macrophages altered the payload of their released EVs, including RNA-binding proteins, molecular motors, and proteins regulating secretory pathways. A wound-healing model demonstrated that closure was delayed by EVs released under the control of TBC1D3. We show that modulating the secretory repertoire of a cell regulates EV payload and biologic activity that affects outcomes in tissue repair and establishes a strategy for modifying EVs mediating specific biologic responses.-Qin, S., Dorschner, R. A., Masini, I., Lavoie-Gagne, O., Stahl, P. D., Costantini, T. W., Baird, A., Eliceiri, B. P. TBC1D3 regulates the payload and biological activity of extracellular vesicles that mediate tissue repair.
健康的皮肤损伤修复是炎症细胞、分泌因子和生物活性细胞外囊泡（EVs）的协调反应。虽然 EVs 在生物体液中的组成性释放是培养细胞和肿瘤的标志，但它们的有效载荷和生物活性似乎受到严格调节。我们发现 Tre-2/Bub2/Cdc16（TBC1）结构域家族成员 3（TBC1D3）驱动 EV 群体的释放，导致未成熟受体细胞中转录因子信号转导和转录激活因子 3 的磷酸化减少。为了探索 EVs 的生物学活性，我们使用无菌皮下炎症的小鼠模型来确定由定向髓系谱系和基质释放到微环境中的 EVs 的有效载荷和生物学活性。巨噬细胞中 TBC1D3 的表达改变了其释放的 EVs 的有效载荷，包括 RNA 结合蛋白、分子马达和调节分泌途径的蛋白质。伤口愈合模型表明，在 TBC1D3 控制下释放的 EV 会延迟闭合。我们表明，调节细胞的分泌谱可调节 EV 的有效载荷和生物学活性，从而影响组织修复的结果，并为修饰介导特定生物学反应的 EV 建立了一种策略。-秦，S.，Dorschner，R. A.，马西尼，I.，拉沃伊-加涅，O.，施塔尔，P. D.，科斯坦蒂尼，T. W.，贝尔德，A.，埃利塞里，B. P. TBC1D3 调节介导组织修复的细胞外囊泡的有效载荷和生物学活性。
