Identification of therapeutic target genes involved in skeletal muscle atrophy in space through epigenomics

Research Project

Project/Area Number	17H06548
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Single-year Grants
Research Field	Integrative animal science
Research Institution	Japan Aerospace EXploration Agency (2018) University of Tsukuba (2017)
Principal Investigator	Okada Risa 国立研究開発法人宇宙航空研究開発機構, 有人宇宙技術部門, 研究開発員 (20803498)
Project Period (FY)	2017-08-25 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	骨格筋 / 微小重力 / エピゲノム / 国際宇宙ステーション（ISS） / 国際宇宙ステーション (ISS) / 国際宇宙ステーション(ISS)
Outline of Final Research Achievements	Skeletal muscle is one of the most robustly affected organs under different gravitational conditions and it is known that space environment causes muscle weakness, however the molecular mechanism of muscle atrophy in space is largely unknown. To reveal the molecular mechanism of muscle atrophy, we conducted transcriptome and epigenetics analysis of soleus muscles of mice housed under microgravity or artificial-1g in space to measure the gene expression and epigenetic modification patterns, resulting a significantly up- or down-regulation of genes in MG mice compared with AG mice. To examine the relations of these genes and muscle atrophy, we introduced some of them into C2C12 myotubes using recombinant adenovirus vectors and identified several genes as candidates that cause a reduction in myotube diameter. These results suggest that candidate genes that we found through the comprehensive analysis and in vitro screening may have roles in microgravity-induced muscle atrophy.
Academic Significance and Societal Importance of the Research Achievements	骨格筋萎縮は、寝たきりなどの不活動（廃用性萎縮）や加齢に伴う老化（サルコペニア）などが原因で生じ、骨格筋としての機能は著しく障害される。近年、高齢化社会を迎えている我が国では骨格筋萎縮は解決すべき大きな社会問題の１つであるにもかかわらず、有効な予防法、治療法は未だ確立されていない。本研究では、宇宙環境で起こるエピゲノム変化を伴う発現変動遺伝子に着目し、筋委縮を誘導し持続させる候補遺伝子を見出すことで、これらの遺伝子の今後の治療標的としての可能性を示唆した。