Dataset Information

Proteomics Identifies Differences in Fibrotic Potential of Exosomes from Human Tendon and Muscle Fibroblasts

ABSTRACT: Fibroblasts are the powerhouses responsible for the production and assembly of extracellular matrix. Their activity needs to be tightly controlled especially within the musculoskeletal system, where changes to extracellular matrix composition affect force transmission and mechanical loading that are required for effective movement of the body. Extracellular vesicles, including exosomes, 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 extracellular vesicles is during tissue homeostasis. Here, we performed proteomic analysis of exosomes derived from primary human muscle and tendon cells to identify the potential functions of healthy fibroblast-derived exosomes. Mass spectrometry-based proteomics revealed comprehensive profiles for exosomes released from healthy human fibroblasts from different tissues. We found that fibroblast-derived exosomes were more similar than exosomes from differentiating myoblasts, but there were significant differences between tendon fibroblasts and muscle fibroblasts exosomes. Exosomes from tendon fibroblasts contain higher levels of proteins that support extracellular matrix synthesis, including TGFβ1, and muscle fibroblast exosomes contain a higher abundance of MMP2. Our data demonstrates a marked heterogeneity among healthy fibroblast-derived exosomes, indicating shared tasks between exosomes of skeletal muscle myoblasts and fibroblast, whereas tendon fibroblast exosomes has a marked fibrotic potential in human tendon tissue. These findings suggest an important role for exosomes in tissue homeostasis of both tendon and skeletal muscle in humans.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Erwin Schoof

LAB HEAD: Michael Kjaer

PROVIDER: PXD018233 | Pride | 2021-09-09

REPOSITORIES: Pride

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Publications

Proteomics identifies differences in fibrotic potential of extracellular vesicles from human tendon and muscle fibroblasts.

Yeung Ching-Yan Chloé CC Schoof Erwin M EM Tamáš Michal M Mackey Abigail L AL Kjaer Michael M

Cell communication and signaling : CCS 20201104 1

<h4>Background</h4>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. How ...[more]

PMID: 33148271

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Project description:Tendon pathologies affect a large portion of people with diabetes. This high rate of tendon pain, injury, and disease appears to manifest independent of well-controlled HbA1c and fasting blood glucose. Advanced glycation end products (AGEs) are elevated in the serum of those with diabetes. In vitro, AGEs severely impact tendon fibroblast proliferation and mitochondrial function. However, the extent that AGEs impact the tendon cell transcriptome has not been evaluated. The purpose of this study was to investigate transcriptome-wide changes that occur to tendon-derived fibroblasts following treatment with AGEs. We propose to complete a descriptive approach to pathway profiling to broaden our mechanistic understanding of cell signaling events that may contribute to the development of tendon pathology. Rat Achilles tendon fibroblasts were treated with glycolaldehyde-derived AGEs (200μg/ml) for 48 hours in normal glucose (5.5mM) conditions. In addition, total RNA was isolated, and the PolyA+ library was sequenced. We demonstrate that tendon fibroblasts treated with 200μg/ml of AGEs differentially express 2,159 gene targets compared to fibroblasts treated with an equal amount of BSA-Control. Additionally, we report in a descriptive and ranked fashion 21 implicated cell-signaling pathways. We demonstrate that tendon fibroblasts treated with 200μg/ml of AGEs differentially express 2,159 gene targets compared to fibroblasts treated with an equal amount of BSA-Control. Additionally, we report in a descriptive and ranked fashion 21 implicated cell-signaling pathways. Our findings suggest that AGEs disrupt the tendon fibroblast transcriptome on a large scale and that these pathways may contribute to the development and progression of diabetic tendinopathy. Specifically, pathways related to cell cycle progression and extracellular matrix remodeling were affected in our data set and may play a contributing role in the development of diabetic tendon complications.

Dataset Information

Proteomics Identifies Differences in Fibrotic Potential of Exosomes from Human Tendon and Muscle Fibroblasts

Publications

Proteomics identifies differences in fibrotic potential of extracellular vesicles from human tendon and muscle fibroblasts.

Similar Datasets

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