Proteomics identifies differences in fibrotic potential of extracellular vesicles from human tendon and muscle fibroblas
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(2020) 18:177
RESEARCH
Open Access
Proteomics identifies differences in fibrotic potential of extracellular vesicles from human tendon and muscle fibroblasts Ching-Yan Chloé Yeung1,2* , Erwin M. Schoof3 , Michal Tamáš1,2, Abigail L. Mackey1,2,4
and Michael Kjaer1,2
Abstract Background: 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 fibroblastderived EVs is during tissue homeostasis. Methods: 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. Results: 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. Conclusions: 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. Keywords: Extracellular vesicle, Musculoskeletal tissue, Mass spectrometry, Extracellular matrix
* Correspondence: [email protected]; [email protected] 1 Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Nielsine Nielsens Vej 11, Building 8, Copenhagen, NV 2400, Denmark 2 Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence
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