Morphological and Molecular Changes in Juvenile Normal Human Fibroblasts Exposed to Simulated Microgravity

Abstract The literature suggests morphological alterations and molecular biological changes within the cellular milieu of human cells, exposed to microgravity (µg), as many cell types assemble to multicellular spheroids (MCS). In this study we investigated juvenile normal human dermal fibroblasts (N...

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Autores principales:	Christoph Buken, Jayashree Sahana, Thomas J. Corydon, Daniela Melnik, Johann Bauer, Markus Wehland, Marcus Krüger, Silke Balk, Nauras Abuagela, Manfred Infanger, Daniela Grimm
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/86477763840b461398e6254deea13733
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spelling	oai:doaj.org-article:86477763840b461398e6254deea137332021-12-02T15:09:13ZMorphological and Molecular Changes in Juvenile Normal Human Fibroblasts Exposed to Simulated Microgravity10.1038/s41598-019-48378-92045-2322https://doaj.org/article/86477763840b461398e6254deea137332019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48378-9https://doaj.org/toc/2045-2322Abstract The literature suggests morphological alterations and molecular biological changes within the cellular milieu of human cells, exposed to microgravity (µg), as many cell types assemble to multicellular spheroids (MCS). In this study we investigated juvenile normal human dermal fibroblasts (NHDF) grown in simulated µg (s-µg) on a random positioning machine (RPM), aiming to study changes in cell morphology, cytoskeleton, extracellular matrix (ECM), focal adhesion and growth factors. On the RPM, NHDF formed an adherent monolayer and compact MCS. For the two cell populations we found a differential regulation of fibronectin, laminin, collagen-IV, aggrecan, osteopontin, TIMP-1, integrin-β1, caveolin-1, E-cadherin, talin-1, vimentin, α-SM actin, TGF-β1, IL-8, MCP-1, MMP-1, and MMP-14 both on the transcriptional and/or translational level. Immunofluorescence staining revealed only slight structural changes in cytoskeletal components. Flow cytometry showed various membrane-bound proteins with considerable variations. In silico analyses of the regulated proteins revealed an interaction network, contributing to MCS growth via signals mediated by integrin-β1, E-cadherin, caveolin-1 and talin-1. In conclusion, s-µg-conditions induced changes in the cytoskeleton, ECM, focal adhesion and growth behavior of NHDF and we identified for the first time factors involved in fibroblast 3D-assembly. This new knowledge might be of importance in tissue engineering, wound healing and cancer metastasis.Christoph BukenJayashree SahanaThomas J. CorydonDaniela MelnikJohann BauerMarkus WehlandMarcus KrügerSilke BalkNauras AbuagelaManfred InfangerDaniela GrimmNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-22 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christoph Buken Jayashree Sahana Thomas J. Corydon Daniela Melnik Johann Bauer Markus Wehland Marcus Krüger Silke Balk Nauras Abuagela Manfred Infanger Daniela Grimm Morphological and Molecular Changes in Juvenile Normal Human Fibroblasts Exposed to Simulated Microgravity
description	Abstract The literature suggests morphological alterations and molecular biological changes within the cellular milieu of human cells, exposed to microgravity (µg), as many cell types assemble to multicellular spheroids (MCS). In this study we investigated juvenile normal human dermal fibroblasts (NHDF) grown in simulated µg (s-µg) on a random positioning machine (RPM), aiming to study changes in cell morphology, cytoskeleton, extracellular matrix (ECM), focal adhesion and growth factors. On the RPM, NHDF formed an adherent monolayer and compact MCS. For the two cell populations we found a differential regulation of fibronectin, laminin, collagen-IV, aggrecan, osteopontin, TIMP-1, integrin-β1, caveolin-1, E-cadherin, talin-1, vimentin, α-SM actin, TGF-β1, IL-8, MCP-1, MMP-1, and MMP-14 both on the transcriptional and/or translational level. Immunofluorescence staining revealed only slight structural changes in cytoskeletal components. Flow cytometry showed various membrane-bound proteins with considerable variations. In silico analyses of the regulated proteins revealed an interaction network, contributing to MCS growth via signals mediated by integrin-β1, E-cadherin, caveolin-1 and talin-1. In conclusion, s-µg-conditions induced changes in the cytoskeleton, ECM, focal adhesion and growth behavior of NHDF and we identified for the first time factors involved in fibroblast 3D-assembly. This new knowledge might be of importance in tissue engineering, wound healing and cancer metastasis.
format	article
author	Christoph Buken Jayashree Sahana Thomas J. Corydon Daniela Melnik Johann Bauer Markus Wehland Marcus Krüger Silke Balk Nauras Abuagela Manfred Infanger Daniela Grimm
author_facet	Christoph Buken Jayashree Sahana Thomas J. Corydon Daniela Melnik Johann Bauer Markus Wehland Marcus Krüger Silke Balk Nauras Abuagela Manfred Infanger Daniela Grimm
author_sort	Christoph Buken
title	Morphological and Molecular Changes in Juvenile Normal Human Fibroblasts Exposed to Simulated Microgravity
title_short	Morphological and Molecular Changes in Juvenile Normal Human Fibroblasts Exposed to Simulated Microgravity
title_full	Morphological and Molecular Changes in Juvenile Normal Human Fibroblasts Exposed to Simulated Microgravity
title_fullStr	Morphological and Molecular Changes in Juvenile Normal Human Fibroblasts Exposed to Simulated Microgravity
title_full_unstemmed	Morphological and Molecular Changes in Juvenile Normal Human Fibroblasts Exposed to Simulated Microgravity
title_sort	morphological and molecular changes in juvenile normal human fibroblasts exposed to simulated microgravity
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/86477763840b461398e6254deea13733
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Morphological and Molecular Changes in Juvenile Normal Human Fibroblasts Exposed to Simulated Microgravity

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