Novel signaling pathway which regulates skeletal muscle regeneration after injury

• Project/Area Number: 26670157
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Kobe University
• Principal Investigator: MINAMI YASUHIRO 神戸大学, 医学(系)研究科(研究院), 教授 (70229772)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Ror1チロシンキナーゼ / 骨格筋損傷修復 / 筋衛星細胞 / 炎症性サイトカイン / 遺伝子発現制御 / 細胞増殖 / 幹細胞性維持 / 受容体型チロシンキナーゼRor1 / Ror1シグナル / 筋分化 / 遺伝子発現誘導 / NF-κB経路

Outline of Final Research Achievements

The skeletal muscle is a highly regenerative tissue and/or organ, and tissue stem cells of the skeletal muscle, designated as skeletal muscle satellite cells (SCs), play important roles during regeneration of the skeletal muscle after its injury. In this study, we found that the receptor tyrosine kinase Ror1 is expressed selectively in SCs, and that expression of Ror1 is further induced by activation of NF-κB pathway which can be elicited by inflammatory cytokines, induced and secreted by immune cells following injury of the skeletal muscle. In this study, we also show that expression of Ror1, induced in SCs, plays an important role in regulating the behavior and function of SCs during regeneration of the skeletal muscle.

Research Products

• [Int'l Joint Research] Harvard University(米国)
• [Journal Article] Wnt5a-Ror2 signaling in mesenchymal stem cells promotes proliferation of gastric cancer cells by activating CXCL16-CXCR6 axis. (2016)
  • Author(s): Takiguchi, G., Nishita, M., Kurita, K., Kakeji, Y., Minami, Y.
  • Journal Title: Cancer Sci. Volume: 107 Issue: 3 Pages: 290-297
  • DOI: 10.1111/cas.12871
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Essential role of Wnt5a-Ror1/Ror2 signaling in metanephric mesenchyme and ureteric bud formation. (2016)
  • Author(s): Qi X, Okinaka Y, Nishita M, Minami Y.
  • Journal Title: Genes to Cells Volume: 21 Issue: 4 Pages: 325-334
  • DOI: 10.1111/gtc.12342
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ROR1 is essential for proper innervation of auditory hair cells and hearing in humans and mice. (2016)
  • Author(s): Diaz-Horta, O., Abad, C., Sennaroglu, L., Foster II, J., DeSmidt, A., Bademci, G., Tokgoz-Yilmaz, S., Duman, D., Cengiz, F. B., Grati, M., Fitoz, S., Liu, X-Z., Farooq, A., Imtiaz, F., Currall, B. B., Morton, C. C., Nishita, M., Minami, Y., Lu, Z., Walz, K., Tekin, M.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Insight into the role of Wnt5a-induced signaling in normal and cancer cells. (2015)
  • Author(s): Endo, M., Nishita, M., Fujii, M., Minami, Y.
  • Journal Title: Int. Rev. Cell Mol. Biol. Volume: 314 Pages: 117-148
  • DOI: 10.1016/bs.ircmb.2014.10.003
  • ISBN: 9780128022832
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The Wnt5a-Ror2 axis promotes the signaling circuit between interleukin-12 and interferon-γ in colitis. (2015)
  • Author(s): Sato, A., Kayama, H., Shojima, K., Matsumoto, S., Koyama, H., Minami, Y., Nojima, S., Morii, E., Honda, H., Takeda, K., Kikuchi, A.
  • Journal Title: Sci. Rep. Volume: 5 Issue: 1 Pages: 10536-10536
  • DOI: 10.1038/srep10536
  • Peer Reviewed / Open Access
• [Journal Article] The Wnt5a-Ror2 axis promotes the signaling circuit between interleukin-12 and interferon-g in colitis. (2015)
  • Author(s): Sato, A., Kayama, H., Shojima, K., Matsumoto, S., Koyama, H., Minami, Y., Nojima, S., Morii, E., Honda, H., Takeda, K., Kikuchi, A.
  • Journal Title: Sci. Report Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Diabetic osteopenia by decreased β-catenin signaling is partly induced by epigenetic derepression of sFRP-4 gene (2014)
  • Author(s): Mori K, Kitazawa R, Kondo T, Mori M, Hamada Y, Nishida M, Minami Y, Haraguchi R, Takahashi Y, Kitazawa S.
  • Journal Title: PLoS One Volume: 9 Issue: 7 Pages: e102797-e102797
  • DOI: 10.1371/journal.pone.0102797
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of Wnt5a-Ror2 signaling in morphogenesis of the metanephric mesenchyme during ureteric budding (2014)
  • Author(s): Nishita M, Qiao S, Miyamoto M, Okinaka Y, Yamada M, Hashimoto R, Iijima K, Otani H, Hartmann C, Nishinakamura R, Minami Y
  • Journal Title: Mol Cell Biol Volume: 34 Issue: 16 Pages: 3096-3105
  • DOI: 10.1128/mcb.00491-14
  • Peer Reviewed / Open Access
• [Presentation] Crucial role of the Ror-family rcceptor tyosine kinases in regulating tissue stem cells (2016)
  • Author(s): Koki Kamizaki, Ryosuke Doi, Takeshi Saji, Mitsuharu Endo, Motoi Kanagawa, So-ichiro Fukada, Tatsushi Toda, Makoto Hayashi, Yasuhiro Minami
  • Organizer: 環太平洋創薬・新規治療標的同定ネットワーク、Kick-off Symposium
  • Place of Presentation: 神戸大学（兵庫県）
  • Year and Date: 2016-03-22
• [Presentation] Wnt5a-Ror2シグナルは繊毛タンパク質IFT20の発現誘導を介してがん細胞の浸潤を制御する (2015)
  • Author(s): 西田 満、西尾 忠、 紙崎 孝基、王 志超、榎本 真宏、玉田 紘太、内匠 透、Victor W. Hsu、Gregory J. Pazour、南 康博
  • Organizer: 第３８回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場（兵庫県）
  • Year and Date: 2015-12-04
• [Presentation] TNFα によって誘導されたRor1は筋芽細胞の増殖を促進する (2015)
  • Author(s): 紙崎 孝基、土井 亮助、加藤 英、佐事 武、遠藤 光晴、金川 基、戸田 達史、深田 宗一朗、林 真琴、南 康博
  • Organizer: 第３８回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場（兵庫県）
  • Year and Date: 2015-12-03
• [Presentation] 受容体型チロシンキナーゼRor2は静止期のアストロサイトが増殖を再開するために必要である (2015)
  • Author(s): 遠藤 光晴、小林 千穂、疋田 壮舞、グリジャハン オブリカスム、稲垣 貴彦、南 康博
  • Organizer: 第３８回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場（兵庫県）
  • Year and Date: 2015-12-02
• [Presentation] 筋再生における Ror1 の役割 (2015)
  • Author(s): 林 真琴、南 康博
  • Organizer: 第１６回運動器科学研究会
  • Place of Presentation: 鹿児島
  • Year and Date: 2015-09-11
• [Presentation] Novel role for Wnt5a-Ror2 signaling in regulating polarity and structure of the Golgi apparatus in osteosarcoma cells. (2015)
  • Author(s): Michiru Nishita, Yasuhiro Minami
  • Organizer: University of Washington-Kobe University Joint Symposium on Cell Signaling
  • Place of Presentation: University of Washington, Seattle, USA
  • Year and Date: 2015-09-10
  • Int'l Joint Research / Invited
• [Presentation] 筋芽細胞におけるRor1のNF-kBを介した発現誘導機構 (2015)
  • Author(s): 紙崎 孝基 、南 康博
  • Organizer: 第7回シグナルネットワーク研究会
  • Place of Presentation: 沖縄県国頭郡恩納村
  • Year and Date: 2015-06-20
• [Presentation] Role of NF-κB-mediated expression of Ror1 during skeletal muscle regeneration (2014)
  • Author(s): Koki Kamisaki, Ryosuke Doi, Suguru Kato, Soichiro Fukada, Motoi Kanagawa, Tatsushi, Mitsuharu Endo, Yasushiro Minami
  • Organizer: UNIVERSITY OF WASHINGTON-KOBE UNIVERSITY INTERNATIONAL SYMPOSIUM ON MEMBRANE BIOLOGY
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2014-12-15
• [Presentation] 受容体型チロシンキナーゼRor1による骨格筋再生制御 (2014)
  • Author(s): 加藤 英、土井 亮助、遠藤 光晴、深田 宗一郎、金川 基、戸田 達史、南 康博
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-27
• [Book] Receptor Tyrosine Kinases: Family and Subfamilies (2015)
  • Author(s): Endo, M., Nishita, M., Doi, R., Hayashi, M., Minami, Y.
  • Total Pages: 878
  • Publisher: Springer Science
• [Book] ROR Receptor Tyrosine Kinase Family (Chapter 13) Receptor Tyrosine Kinases: Family and subfamilies (2015)
  • Author(s): Endo, M., Nishita, M., Doi, R., Hayashi, M., Minami, Y.
  • Publisher: Springer Science
• [Remarks] http://www.med.kobe-u.ac.jp/medzoo/
• [Remarks] 研究室ホームページ
  • URL: http://www.med.kobe-u.ac.jp/medzoo/