title: Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts.
abstract: Microgravity and cosmic rays as found in space are difficult to recreate on earth. However, ground-based models exist to simulate space flight experiments. In the present study, an experimental model was utilized to monitor gene expression changes in fetal skin fibroblasts of murine origin. Cells were continuously subjected for 65 h to a low dose (55 mSv) of ionizing radiation (IR), comprising a mixture of high‑linear energy transfer (LET) neutrons and low-LET gamma-rays, and/or simulated microgravity using the random positioning machine (RPM), after which microarrays were performed. The data were analyzed both by gene set enrichment analysis (GSEA) and single gene analysis (SGA). Simulated microgravity affected fetal murine fibroblasts by inducing oxidative stress responsive genes. Three of these genes are targets of the nuclear factor‑erythroid 2 p45-related factor 2 (Nrf2), which may play a role in the cell response to simulated microgravity. In addition, simulated gravity decreased the expression of genes involved in cytoskeleton remodeling, which may have been caused by the downregulation of the serum response factor (SRF), possibly through the Rho signaling pathway. Similarly, chronic exposure to low-dose IR caused the downregulation of genes involved in cytoskeleton remodeling, as well as in cell cycle regulation and DNA damage response pathways. Many of the genes or gene sets that were altered in the individual treatments (RPM or IR) were not altered in the combined treatment (RPM and IR), indicating a complex interaction between RPM and IR.
authors.affiliation: Radiobiology Unit, Expert Group of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK-CEN), Mol, Belgium.
authors.forename: Michaël
authors.initials: M
authors.lastname: Beck
authors.affiliation: Radiobiology Unit, Expert Group of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK-CEN), Mol, Belgium.
authors.forename: Marjan
authors.initials: M
authors.lastname: Moreels
authors.affiliation: Radiobiology Unit, Expert Group of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK-CEN), Mol, Belgium.
authors.forename: Roel
authors.initials: R
authors.lastname: Quintens
authors.affiliation: Radiobiology Unit, Expert Group of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK-CEN), Mol, Belgium.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abou-El-Ardat
authors.affiliation: Radiobiology Unit, Expert Group of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK-CEN), Mol, Belgium.
authors.forename: Hussein
authors.initials: H
authors.lastname: El-Saghire
authors.affiliation: Radiobiology Unit, Expert Group of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK-CEN), Mol, Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Tabury
authors.affiliation: Radiobiology Unit, Expert Group of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK-CEN), Mol, Belgium.
authors.forename: Arlette
authors.initials: A
authors.lastname: Michaux
authors.affiliation: Radiobiology Unit, Expert Group of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK-CEN), Mol, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Janssen
authors.affiliation: Radiobiology Unit, Expert Group of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK-CEN), Mol, Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Neefs
authors.affiliation: Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Oostveldt
authors.affiliation: Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.
authors.forename: Winnok H
authors.initials: WH
authors.lastname: De Vos
authors.affiliation: Radiobiology Unit, Expert Group of Molecular and Cellular Biology, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK-CEN), Mol, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Baatout
mesh_terms: D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism* / Q000473:pathology; D005333:Fetus / Q000528:radiation effects; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D005786:Gene Expression Regulation; D051379:Mice; D008870:Microtubules / Q000378:metabolism / Q000528:radiation effects; D018384:Oxidative Stress / Q000235:genetics* / Q000528:radiation effects; D011839:Radiation, Ionizing; D013026:Space Flight; D018474:Weightlessness Simulation