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Exploring the Effects of Spaceflight on Mouse Physiology using the Open Access NASA GeneLab Platform
Published on: January 13, 2019
Genetic and Apoptotic Changes in Lungs of Mice Flown on the STS-135 Mission in Space
Daila S Gridley1, Xiao Wen Mao2, Jian Tian2
1Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A. dgridley@llu.edu.
Aim:
The goal of the study was to evaluate changes in lung status due to spaceflight stressors that include radiation above levels found on Earth.
Materials And 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.
Conclusion:
The results demonstrate that spaceflight-related stress had a significant impact on lung integrity, indicative of tissue injury and remodeling.

