Fibroblasts are the powerhouses responsible for the production and assembly of extracellular matrix (ECM). Their activity needs to be tightly controlled especially within the musculoskeletal system, where changes to ECM composition affect force transmission and mechanical loading that are required for effective movement of the body. Extracellular vesicles (EVs) are a mode of cell-cell communication within and between tissues, which has been largely characterised in cancer. However, it is unclear what the role of healthy fibroblast-derived EVs is during tissue homeostasis. Here, we performed proteomic analysis of small EVs derived from primary human muscle and tendon cells to identify the potential functions of healthy fibroblast-derived EVs. Mass spectrometry-based proteomics revealed comprehensive profiles for small EVs released from healthy human fibroblasts from different tissues. We found that fibroblast-derived EVs were more similar than EVs from differentiating myoblasts, but there were significant differences between tendon fibroblast and muscle fibroblast EVs. Small EVs from tendon fibroblasts contained higher levels of proteins that support ECM synthesis, including TGFβ1, and muscle fibroblast EVs contained proteins that support myofiber function and components of the skeletal muscle matrix. Our data demonstrates a marked heterogeneity among healthy fibroblast-derived EVs, indicating shared tasks between EVs of skeletal muscle myoblasts and fibroblasts, whereas tendon fibroblast EVs could play a fibrotic role in human tendon tissue. These findings suggest an important role for EVs in tissue homeostasis of both tendon and skeletal muscle in humans.

中文翻译：

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蛋白质组学确定来自人肌腱和肌肉成纤维细胞的细胞外囊泡的纤维化潜力差异

成纤维细胞是负责生产和组装细胞外基质 (ECM) 的动力源。他们的活动需要受到严格控制，尤其是在肌肉骨骼系统内，ECM 成分的变化会影响身体有效运动所需的力传递和机械负荷。细胞外囊泡 (EV) 是一种组织内部和组织之间的细胞间通讯模式，其主要特征是在癌症中。然而，尚不清楚健康成纤维细胞衍生的 EV 在组织稳态过程中的作用。在这里，我们对源自原代人类肌肉和肌腱细胞的小 EV 进行了蛋白质组学分析，以确定健康的成纤维细胞来源的 EV 的潜在功能。基于质谱的蛋白质组学揭示了来自不同组织的健康人成纤维细胞释放的小 EV 的综合特征。我们发现成纤维细胞衍生的 EVs 比分化成肌细胞的 EVs 更相似，但肌腱成纤维细胞和肌肉成纤维细胞 EVs 之间存在显着差异。来自肌腱成纤维细胞的小 EV 包含更高水平的支持 ECM 合成的蛋白质，包括 TGFβ1，而肌肉成纤维细胞 EV 包含支持肌纤维功能和骨骼肌基质成分的蛋白质。我们的数据表明健康成纤维细胞来源的 EVs 之间存在显着的异质性，表明骨骼肌成肌细胞和成纤维细胞的 EVs 之间共享任务，而肌腱成纤维细胞 EVs 可以在人类肌腱组织中发挥纤维化作用。