The role of UPR in preservation of skeletal muscle

• Project/Area Number: 16K10836
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Shokei Gakuin College
• Principal Investigator: Tohmonda Takahide 尚絅学院大学, 総合人間科学系, 准教授 (40415237)
• Research Collaborator: Horiuchi Keisuke ; Yoda Masaki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 小胞体ストレス / 筋骨格系 / XBP1

Outline of Final Research Achievements

To know the role of endoplasmic reticulum stress response pathway in skeletal muscle, skeletal muscle tissues in IRE1a gene deficient mice, in which skeletal muscle-specificthat muscle atrophy was occurring, was subjected to functional analysis.
I examined the relationship between the endoplasmic reticulum stress response pathway and muscle atrophy, and it was indicated that the expression of foxo1 gene was significantly increased in IRE1a deficient mouse. In this study, it was confirmed that the factor induced by activation of endoplasmic reticulum stress sensor is linked to the promoter region of foxo1 gene and regulated the transcription of it.I revealed that the endoplasmic reticulum stress sensor is involved in the process of muscle atrophy.

Academic Significance and Societal Importance of the Research Achievements

超高齢社会を迎えた日本社会では、高齢者の方々の運動器の機能を保全することは、重要な課題である。中でも骨格筋は、生活に必要な所動作のすべてを規定してしまうため、この機能を保全することは、生活の質を保つために特に重要となる。本研究では骨格筋機能維持の新規システム、特に小胞体ストレス応答経路を介した筋特異的生理機能維持システムの一端を明らかにし、骨格筋委縮や筋不全、また骨格筋に由来する糖尿病・メタボリックシンドロームなどに対する、新しい予防法及び改善法開発へ向けた基礎的基盤の提供を行った。

Research Products

• [Journal Article] Identification and characterization of novel conserved domains in metazoan Zic proteins. (2018)
  • Author(s): Tohmonda, T., Kamiya, A., Ishiguro, A., Iwaki, T., Fujimi, T.J., Hatayama, M., Aruga, J.
  • Journal Title: Mol Biol Evol Volume: 35 Issue: 9 Pages: 2205-2229
  • DOI: 10.1093/molbev/msy122
  • Peer Reviewed
• [Journal Article] An Evolutionarily Conserved Mesodermal Enhancer in Vertebrate Zic3. (2018)
  • Author(s): Odaka YS, Tohmonda T, Toyoda A, Aruga J.
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 14954-14954
  • DOI: 10.1038/s41598-018-33235-y
  • Peer Reviewed / Open Access
• [Journal Article] The unfolded protein response in skeletal development and homeostasis (2016)
  • Author(s): Horiuchi K, Tohmonda T, Morioka H
  • Journal Title: Cell and Molecular Life Science Volume: na Issue: 15 Pages: 2851-69
  • DOI: 10.1007/s00018-016-2178-1
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Conditional abrogation of Atm in osteoclasts extends osteoclast lifespan and results in reduced bone mass (2016)
  • Author(s): Hirozane T, Tohmonda T, Yoda M, Shimoda M, Kanai Y, Matsumoto M, Morioka H, Nakamura M, Horiuchi K.
  • Journal Title: Scientific Reports Volume: － Issue: 1 Pages: 34426-34426
  • DOI: 10.1038/srep34426
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Corrigendum: Novel method for immunofluorescence staining of mammalian eggs using non-contact alternating- current electric- field mixing of microdroplets. (2016)
  • Author(s): Shirasawa H, Kumagai J, Sato E, Kabashima K, Kumazawa Y, Sato W, Miura H, Nakamura R, Nanjo H, Minamiya Y, Akagami Y, Terada Y.
  • Journal Title: Scientic Reports Volume: 7 Issue: 1 Pages: 6-6
  • DOI: 10.1038/srep41552
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] IRE1a-XBP1経路を基軸とした骨代謝制御 (2017)
  • Author(s): 東門田 誠一
  • Organizer: 第40回日本分子生物学会、生命科学系学会合同年次大会
  • Invited