Tridimensional cell culture of dermal fibroblasts promotes exosome-mediated secretion of extracellular matrix proteins

Abstract Extracellular matrix (ECM) secretion, deposition and assembly are part of a whole complex biological process influencing the microenvironment and other cellular behaviors. Emerging evidence is attributing a significant role to extracellular vesicles (EVs) and exosomes in a plethora of ECM-a...

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Main Authors: Vincent Clément, Vincent Roy, Bastien Paré, Cassandra R. Goulet, Lydia Touzel Deschênes, François Berthod, Stéphane Bolduc, François Gros-Louis
Format: Article
Language:English
Published: Nature Portfolio 2022-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-23433-0
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author Vincent Clément
Vincent Roy
Bastien Paré
Cassandra R. Goulet
Lydia Touzel Deschênes
François Berthod
Stéphane Bolduc
François Gros-Louis
author_facet Vincent Clément
Vincent Roy
Bastien Paré
Cassandra R. Goulet
Lydia Touzel Deschênes
François Berthod
Stéphane Bolduc
François Gros-Louis
author_sort Vincent Clément
collection DOAJ
description Abstract Extracellular matrix (ECM) secretion, deposition and assembly are part of a whole complex biological process influencing the microenvironment and other cellular behaviors. Emerging evidence is attributing a significant role to extracellular vesicles (EVs) and exosomes in a plethora of ECM-associated functions, but the role of dermal fibroblast-derived EVs in paracrine signalling is yet unclear. Herein, we investigated the effect of exosomes isolated from stimulated human dermal fibroblasts. We report that tridimensional (3D) cell culture of dermal fibroblasts promotes secretion of exosomes carrying a large quantity of proteins involved in the formation, organisation and remodelling of the ECM. In our 3D model, gene expression was highly modulated and linked to ECM, cellular migration and proliferation, as well as inflammatory response. Mass spectrometry analysis of exosomal proteins, isolated from 3D cultured fibroblast-conditioned media, revealed ECM protein enrichment, of which many were associated with the matrisome. We also show that the cytokine interleukin 6 (IL-6) is predicted to be central to the signalling pathways related to ECM formation and contributing to cell migration and proliferation. Overall, our data suggest that dermal fibroblast-derived EVs participate in many steps of the establishment of dermis’s ECM.
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spelling doaj.art-0efe0755bb7f43bbbf515dee16de8c322022-12-22T02:52:00ZengNature PortfolioScientific Reports2045-23222022-11-0112111610.1038/s41598-022-23433-0Tridimensional cell culture of dermal fibroblasts promotes exosome-mediated secretion of extracellular matrix proteinsVincent Clément0Vincent Roy1Bastien Paré2Cassandra R. Goulet3Lydia Touzel Deschênes4François Berthod5Stéphane Bolduc6François Gros-Louis7Department of Surgery, Faculty of Medicine, Laval UniversityDepartment of Surgery, Faculty of Medicine, Laval UniversityDepartment of Surgery, Faculty of Medicine, Laval UniversityDepartment of Surgery, Faculty of Medicine, Laval UniversityDepartment of Surgery, Faculty of Medicine, Laval UniversityDepartment of Surgery, Faculty of Medicine, Laval UniversityDepartment of Surgery, Faculty of Medicine, Laval UniversityDepartment of Surgery, Faculty of Medicine, Laval UniversityAbstract Extracellular matrix (ECM) secretion, deposition and assembly are part of a whole complex biological process influencing the microenvironment and other cellular behaviors. Emerging evidence is attributing a significant role to extracellular vesicles (EVs) and exosomes in a plethora of ECM-associated functions, but the role of dermal fibroblast-derived EVs in paracrine signalling is yet unclear. Herein, we investigated the effect of exosomes isolated from stimulated human dermal fibroblasts. We report that tridimensional (3D) cell culture of dermal fibroblasts promotes secretion of exosomes carrying a large quantity of proteins involved in the formation, organisation and remodelling of the ECM. In our 3D model, gene expression was highly modulated and linked to ECM, cellular migration and proliferation, as well as inflammatory response. Mass spectrometry analysis of exosomal proteins, isolated from 3D cultured fibroblast-conditioned media, revealed ECM protein enrichment, of which many were associated with the matrisome. We also show that the cytokine interleukin 6 (IL-6) is predicted to be central to the signalling pathways related to ECM formation and contributing to cell migration and proliferation. Overall, our data suggest that dermal fibroblast-derived EVs participate in many steps of the establishment of dermis’s ECM.https://doi.org/10.1038/s41598-022-23433-0
spellingShingle Vincent Clément
Vincent Roy
Bastien Paré
Cassandra R. Goulet
Lydia Touzel Deschênes
François Berthod
Stéphane Bolduc
François Gros-Louis
Tridimensional cell culture of dermal fibroblasts promotes exosome-mediated secretion of extracellular matrix proteins
Scientific Reports
title Tridimensional cell culture of dermal fibroblasts promotes exosome-mediated secretion of extracellular matrix proteins
title_full Tridimensional cell culture of dermal fibroblasts promotes exosome-mediated secretion of extracellular matrix proteins
title_fullStr Tridimensional cell culture of dermal fibroblasts promotes exosome-mediated secretion of extracellular matrix proteins
title_full_unstemmed Tridimensional cell culture of dermal fibroblasts promotes exosome-mediated secretion of extracellular matrix proteins
title_short Tridimensional cell culture of dermal fibroblasts promotes exosome-mediated secretion of extracellular matrix proteins
title_sort tridimensional cell culture of dermal fibroblasts promotes exosome mediated secretion of extracellular matrix proteins
url https://doi.org/10.1038/s41598-022-23433-0
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