title: Genetic and Apoptotic Changes in Lungs of Mice Flown on the STS-135 Mission in Space.
abstract: OBJECTIVE
  The goal of the study was to evaluate changes in lung status due to spaceflight stressors that include radiation above levels found on Earth.
  
  
  METHODS
  Within hours after return from a 13-day mission in space onboard the Space Shuttle Atlantis, C57BL/6 mice (FLT group) were euthanized; mice housed on the ground in similar animal enclosure modules served as controls (AEM group). Lung tissue was collected to evaluate the expression of genes related to extracellular matrix (ECM)/adhesion and stem cell signaling. Pathway analysis was also performed. In addition, immunohistochemistry for stem cell antigen-1 (SCA-1), the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay for apoptosis, and staining for histological characteristics were performed.
  
  
  RESULTS
  There were 18/168 genes significantly modulated in lungs from the FLT group (p<0.05 vs. AEM); 17 of these were up-regulated and one was down-regulated. The greatest effect, namely a 5.14-fold increase, was observed on Spock1 (also known as Spark/osteonectin), encoding a multi-functional protein that has anti-adhesive effects, inhibits cell proliferation and regulates activity of certain growth factors. Additional genes with increased expression were cadherin 3 (Cdh3), collagen, type V, alpha 1 (Col5a1), integrin alpha 5 (Itga5), laminin, gamma 1 (Lamc1), matrix metallopeptidase 14 (Mmp14), neural cell adhesion molecule 1 (Ncam1), transforming growth factor, beta induced (Tgfbi), thrombospondin 1 (Thbs1), Thbs2, versican (Vcan), fibroblast growth factor receptor 1 (Fgfr1), frizzled homolog 6 (Fzd6), nicastrin (Ncstn), nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 (Nfatc4), notch gene homolog 4 (Notch4) and vang-like 2 (Vangl2). The down-regulated gene was Mmp13. Staining for SCA-1 protein showed strong signal intensity in bronchiolar epithelial cells of FLT mice (p<0.05 vs. AEM). TUNEL positivity was also significantly higher in the FLT mice (p<0.05 vs. AEM), but no consistent histological differences were noted.
  
  
  CONCLUSIONS
  The results demonstrate that spaceflight-related stress had a significant impact on lung integrity, indicative of tissue injury and remodeling.
authors.affiliation: Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A. dgridley@llu.edu.
authors.forename: Daila S
authors.initials: DS
authors.lastname: Gridley
authors.affiliation: Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.
authors.forename: Xiao Wen
authors.initials: XW
authors.lastname: Mao
authors.affiliation: Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.
authors.forename: Jian
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Human Anatomy & Pathology, Loma Linda University and Medical Center, Loma Linda, CA, U.S.A.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Cao
authors.affiliation: Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.
authors.forename: Celso
authors.initials: C
authors.lastname: Perez
authors.affiliation: BioServe Space Technologies, Aerospace Engineering Sciences, University of Colorado, Boulder, CO, U.S.A.
authors.forename: Louis S
authors.initials: LS
authors.lastname: Stodieck
authors.affiliation: Department of Mechanical Engineering, University of Colorado, Boulder, CO, U.S.A.
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Ferguson
authors.affiliation: Department of Bioengineering, University of North Carolina, Chapel Hill, NC, U.S.A.
authors.forename: Ted A
authors.initials: TA
authors.lastname: Bateman
authors.affiliation: Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pecaut
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D015398:Signal Transduction; D013026:Space Flight; D013234:Stem Cells / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D015815:Cell Adhesion Molecules
keywords: Spaceflight; cell adhesion; extracellular matrix; gene expression; respiratory tract