Fibroblast Differentiation and Matrix Remodeling Impaired under Simulated Microgravity in 3D Cell Culture Model

Exposure to microgravity affects astronauts’ health in adverse ways. However, less is known about the extent to which fibroblast differentiation during the wound healing process is affected by the lack of gravity. One of the key steps of this process is the differentiation of fibroblasts into myofib...

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Autores principales:	Jiranuwat Sapudom, Mei ElGindi, Marc Arnoux, Nizar Drou, Anna Garcia-Sabaté, Jeremy C. M. Teo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	microgravity 3D cell culture fibroblast differentiation tissue repair matrix remodeling Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/85cf52ee0acd4b3ca9e53fdf442a361c
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spelling	oai:doaj.org-article:85cf52ee0acd4b3ca9e53fdf442a361c2021-11-11T17:19:36ZFibroblast Differentiation and Matrix Remodeling Impaired under Simulated Microgravity in 3D Cell Culture Model10.3390/ijms2221119111422-00671661-6596https://doaj.org/article/85cf52ee0acd4b3ca9e53fdf442a361c2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11911https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Exposure to microgravity affects astronauts’ health in adverse ways. However, less is known about the extent to which fibroblast differentiation during the wound healing process is affected by the lack of gravity. One of the key steps of this process is the differentiation of fibroblasts into myofibroblasts, which contribute functionally through extracellular matrix production and remodeling. In this work, we utilized collagen-based three-dimensional (3D) matrices to mimic interstitial tissue and studied fibroblast differentiation under simulated microgravity (sµG). Our results demonstrated that alpha-smooth muscle actin (αSMA) expression and translocation of Smad2/3 into the cell nucleus were reduced upon exposure to sµG compared to the 1<i>g</i> control, which suggests the impairment of fibroblast differentiation under sµG. Moreover, matrix remodeling and production were decreased under sµG, which is in line with the impaired fibroblast differentiation. We further investigated changes on a transcriptomic level using RNA sequencing. The results demonstrated that sµG has less effect on fibroblast transcriptomes, while sµG triggers changes in the transcriptome of myofibroblasts. Several genes and biological pathways found through transcriptome analysis have previously been reported to impair fibroblast differentiation. Overall, our data indicated that fibroblast differentiation, as well as matrix production and remodeling, are impaired in 3D culture under sµG conditions.Jiranuwat SapudomMei ElGindiMarc ArnouxNizar DrouAnna Garcia-SabatéJeremy C. M. TeoMDPI AGarticlemicrogravity3D cell culturefibroblast differentiationtissue repairmatrix remodelingBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11911, p 11911 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microgravity 3D cell culture fibroblast differentiation tissue repair matrix remodeling Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	microgravity 3D cell culture fibroblast differentiation tissue repair matrix remodeling Biology (General) QH301-705.5 Chemistry QD1-999 Jiranuwat Sapudom Mei ElGindi Marc Arnoux Nizar Drou Anna Garcia-Sabaté Jeremy C. M. Teo Fibroblast Differentiation and Matrix Remodeling Impaired under Simulated Microgravity in 3D Cell Culture Model
description	Exposure to microgravity affects astronauts’ health in adverse ways. However, less is known about the extent to which fibroblast differentiation during the wound healing process is affected by the lack of gravity. One of the key steps of this process is the differentiation of fibroblasts into myofibroblasts, which contribute functionally through extracellular matrix production and remodeling. In this work, we utilized collagen-based three-dimensional (3D) matrices to mimic interstitial tissue and studied fibroblast differentiation under simulated microgravity (sµG). Our results demonstrated that alpha-smooth muscle actin (αSMA) expression and translocation of Smad2/3 into the cell nucleus were reduced upon exposure to sµG compared to the 1<i>g</i> control, which suggests the impairment of fibroblast differentiation under sµG. Moreover, matrix remodeling and production were decreased under sµG, which is in line with the impaired fibroblast differentiation. We further investigated changes on a transcriptomic level using RNA sequencing. The results demonstrated that sµG has less effect on fibroblast transcriptomes, while sµG triggers changes in the transcriptome of myofibroblasts. Several genes and biological pathways found through transcriptome analysis have previously been reported to impair fibroblast differentiation. Overall, our data indicated that fibroblast differentiation, as well as matrix production and remodeling, are impaired in 3D culture under sµG conditions.
format	article
author	Jiranuwat Sapudom Mei ElGindi Marc Arnoux Nizar Drou Anna Garcia-Sabaté Jeremy C. M. Teo
author_facet	Jiranuwat Sapudom Mei ElGindi Marc Arnoux Nizar Drou Anna Garcia-Sabaté Jeremy C. M. Teo
author_sort	Jiranuwat Sapudom
title	Fibroblast Differentiation and Matrix Remodeling Impaired under Simulated Microgravity in 3D Cell Culture Model
title_short	Fibroblast Differentiation and Matrix Remodeling Impaired under Simulated Microgravity in 3D Cell Culture Model
title_full	Fibroblast Differentiation and Matrix Remodeling Impaired under Simulated Microgravity in 3D Cell Culture Model
title_fullStr	Fibroblast Differentiation and Matrix Remodeling Impaired under Simulated Microgravity in 3D Cell Culture Model
title_full_unstemmed	Fibroblast Differentiation and Matrix Remodeling Impaired under Simulated Microgravity in 3D Cell Culture Model
title_sort	fibroblast differentiation and matrix remodeling impaired under simulated microgravity in 3d cell culture model
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/85cf52ee0acd4b3ca9e53fdf442a361c
work_keys_str_mv	AT jiranuwatsapudom fibroblastdifferentiationandmatrixremodelingimpairedundersimulatedmicrogravityin3dcellculturemodel AT meielgindi fibroblastdifferentiationandmatrixremodelingimpairedundersimulatedmicrogravityin3dcellculturemodel AT marcarnoux fibroblastdifferentiationandmatrixremodelingimpairedundersimulatedmicrogravityin3dcellculturemodel AT nizardrou fibroblastdifferentiationandmatrixremodelingimpairedundersimulatedmicrogravityin3dcellculturemodel AT annagarciasabate fibroblastdifferentiationandmatrixremodelingimpairedundersimulatedmicrogravityin3dcellculturemodel AT jeremycmteo fibroblastdifferentiationandmatrixremodelingimpairedundersimulatedmicrogravityin3dcellculturemodel
_version_	1718432128609288192

Fibroblast Differentiation and Matrix Remodeling Impaired under Simulated Microgravity in 3D Cell Culture Model

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