Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Effect of a 91 day long stay in weightlessness on the International Space Station on mouse skin physiology

ABSTRACT: Comparitive gene expression in skin between mice maintained in microgravity (0g) and normogravity (1g) environment. Six male C57Bl/J10 mice were housed for 91 days in the specially designed \Mouse Drawer System\ in weightlessness aboard the International Space Station. Three wild-type mice (WT) and three transgenic mice overexpressing the osteogneic factor PTN/OSF1 under the control of the human bone specific ostecalcin promoter (Tg) were used in the experiment. During the 3-month stay on the ISS, 3 mice unfortunately died leaving 2 Tg and 1 WT. \MDS tissue sharing program\ allowed several teams to study various tissues from these mice. Our aim was to investigate the effect of such a long period of microgravity on skin physiology by morphological, biochemical and genomewide analyses by comparison to similar mice on ground. Gene expression in the skin of 3 space mice and of 3 ground mice was analyzed by microarray. As this unique experiment performed on 3 mice limits the power of statistical analyis, as the transgene PTN/OSF1 was not overexpressed in skin and as a pair wise Pearson's correlation rates between the individual levels of expressed transcripts in the WT and the Tg mice were not significantly different from each other in one experimental group (space or ground), data from the 3 mice were combined to compare results from the space an ground groups.

INSTRUMENT(S): Mouse Drawer System, Scanner Genechip 3000 7G

ORGANISM(S): Mus musculus

SUBMITTER: Betty Nusgens

PROVIDER: E-MTAB-2871 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The Ca2+/calmodulin-dependent kinase II is expressed in smooth muscle and believed to mediate intracellular calcium handling and calcium-dependent gene transcription. CaMKII is activated by Angiotensin-II. The multifunctional calcium/calmodulin-dependent kinase II (CaMKII) is activated by Angiotensin-II (Ang-II) in vascular smooth muscle cells (VSMC), but its impact on hypertension remains unknown. In our transgenic mice that express the inhibitor peptide CaMKIIN in smooth muscle (TG SM-CaMKIIN), the blood pressure response to chronic Ang-II infusion was significantly reduced as compared to littermate controls. Surprisingly, examination of blood pressure and heart rate under ganglionic blockade revealed a key role for VSMC CaMKII in efferent sympathetic outflow in response to Ang II hypertension. Consistently, the efferent splanchnic nerve activity and plasma phenylephrine concentrations were significantly lower in TG SM-CaMKIIN mice as compared to littermates. Moreover, the aortic depressor nerve activity was reset in hypertensive wild type animals, but not in TG SM-CaMKIIN mice, suggesting that changes in baroreceptor wall activity may be responsible for the blood pressure difference in Ang-II hypertension. The pulse wave velocity, a measure of vascular wall stiffness in vivo, was increased in aortas of hypertensive compared to normotensive WT animals. However, Ang-II infusion did not alter the pulse wave velocity in transgenic mice, suggesting that CaMKII in VSMC controls structural smooth muscle genes. Accordingly, analysis of gene expression changes in aortas from wild type and TG SM-CaMKIIN hypertensive mice demonstrated that CaMKII inhibition mainly altered the expression of muscle contractile proteins. In contrast, TG SM-CaMKIIN aortas were protected from the Ang-II induced upregulation of genes linked to proliferation, suggesting that CaMKII inhibition prevents the Ang-II-induced reprogramming of smooth muscle cell gene expression towards a proliferative phenotype. 5 WT C57Bl/6 and 5 mice that express the Ca2+/calmodulin-dependent kinase II peptide inhibitor CaMKIIN in smooth muscle only (TG SM-CaMKIIN) were infused with 1.25 ug/kg/min Angiotensin-II by osmotic minipump for 14 days. 5 WT and 5 transgenic mice infused with normal saline served as controls. The mice were sacrificed on day 14 and the thoracic aortas isolated. RNA was isolated and pooled for the following groups: WT (wild type), C (TG SM-CaMKIIN), WT-A (WT with Angiotensin-II), C-A (TG SM-CaMKIIN + Angiotensin-II)

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Effect of a 91 day long stay in weightlessness on the International Space Station on mouse skin physiology

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