Genetic and molecular analysis of growth retardation caused by growth hormone insensitivity

2012 Fiscal Year Final Research Report

• Project/Area Number: 21591183
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Wakayama Medical University
• Principal Investigator: JING Xuefeng 和歌山県立医科大学, 先端医学研究所, 講師 (70316123)
• Co-Investigator(Kenkyū-buntansha): SAKAGUCHI Kazushige 和歌山県立医科大学, 和歌山県立医科大学, 教授 (60178548) ; SAWADA Takahiro 和歌山県立医科大学, 先端医学研究所.分子医学研究部, 助教 (00382325) ; MIYAJIMA Masayasu 和歌山県立医科大学, 医学部, 助教 (80137257)
• Co-Investigator(Renkei-kenkyūsha): CHIHARA Kazuo 神戸大学, 大学院医・学研究科, 客員教授 (00107955) ; IIDA Keiji 神戸大学, 大学院医・学研究科, 助手 (80324911)
• Project Period (FY): 2009 – 2012
• Keywords: 成長障害

Research Abstract

GH is regarded as an essential hormone for postnatal body growth that mainly works through IGF1 production in liver and other tissues, and the whole signaling process is named GH-IGF1 axis. We identified EphA4 as an essential binding partner of GHR. EphA4 binds to GHR and augments activation of the JAK2/STAT5B pathway. In addition, EphA4 directly binds to and phosphorylates STAT5B. Through these interactions, EphA4 transcriptionally enhances IGF1 production in liver cells as well as in others. Epha4 KO mice show short stature in an Epha4 gene dose-dependent fashion, and respond well to IGF1 but not to GH treatment.

Research Products

• [Journal Article] Ephrin-A1-Mediated Dopaminergic Neurogenesis and Angiogenesis in a Rat Model of Parkinson's Disease (2012)
  • Author(s): Xuefeng Jing, Hideto Miwa, Takahiro Sawada, Ichiro Nakanishi, Tomoyoshi Kondo, Masayasu Miyajima, and Kazushige Sakaguchi
  • Journal Title: PLoS ONE Volume: 7 Pages: 1-14
  • Peer Reviewed
• [Journal Article] Crosstalk of Humoral and Cell-Cell Contact-Mediated Signals in Postnatal Body Growth (2012)
  • Author(s): Xuefeng Jing, Masayasu Miyajima, Takahiro Sawada, Qingfa Chen, Keiji Iida, Kenryo, Furushima, Daiki Arai, Kazuo Chihara, and Kazushige Sakaguchi
  • Journal Title: Cell Reports Volume: 2 Pages: 652-665
  • Peer Reviewed
• [Journal Article] Ternary complex formation of EphA4, FGFR and FRS2 plays an important role in the proliferation of embryonic neural stem/progenitor cells (2010)
  • Author(s): Takahiro Sawada, Xuefeng Jing, Yueqiang Zhang, Emi Shimada, Hideyuki Yokote, Masayasu Miyajima, and Kazushige Sakaguchi
  • Journal Title: Genes Cells Volume: 15 Pages: 297-311
  • Peer Reviewed
• [Journal Article] Involvement of GCMB in the transcriptional regulation of the human parathyroid hormone gene in a parathyroid-derived cell line (2010)
  • Author(s): Masayuki Kawahara, Yasumasa Iwasaki, Kazushige Sakaguchi, Takafumi Taguchi, Mitsuru Nishiyama, Takeshi Nigawara, Machiko Kambayashi, Takahiro Sawada, Xuefeng Jing, Masayasu Miyajima, Yoshio Terada, Kozo Hashimoto, and Toshihoro Suda
  • Journal Title: Effects of calcium and 1,25(OH)2D3 Volume: 47 Pages: 534-541
  • Peer Reviewed
• [Presentation] EphA4 plays an important role in postnatal body growth (2012)
  • Author(s): Daiki Arai, Takahiro Sawada, Xuefeng Jing, Masayasu Miyajima, Qingfa Chen, Kenryo Furushima, Keiji Iida, Kazuo Chihara, and Kazushige Sakaguchi
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2012-12-14
• [Presentation] Functional analysis of EphA4 in corticogenesis using conditional knockout mice (2012)
  • Author(s): Qingfa Chen, Kenryo Furushima, Xuefeng Jing, Masayasu Miyajima, Takahiro.Sawada, Daiki Arai, and Kazushige Sakaguchi
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2012-12-14
• [Presentation] Novel signaling pathways of Eph receptors - Contribution to the stem cell biology and the postnatal body growth (2011)
  • Author(s): Kazushige Sakaguchi, Takahiro Sawada, Xuefeng Jing, Kenryo Furushima, Qingfa Chen, Daiki Arai, and Masayasu Miyajima
  • Organizer: Shandong-Wakayama medical symposium cerebrating the 25th anniversary of friendship
  • Place of Presentation: 中国山東省済南市
  • Year and Date: 2011-11-23
• [Presentation] Ephrin-A1-mediated transformation of subventricular neural stem niche leading to dopaminergic neurogenesis in the dopamine-depleted striatum (poster) (2010)
  • Author(s): Xuefeng Jing, Hideto Miwa, Takahiro Sawada, Ichiro Nakanishi, Tomoyoshi Kondo, Masayasu Miyajima and Kazushige Sakaguchi
  • Organizer: Eph/ephrins and cancer meeting
  • Place of Presentation: Washington-Salem, NC, USA
  • Year and Date: 2010-06-22
• [Presentation] Signaling through the ternary complex of EphA4, FGFR and FRS2 (poster) (2010)
  • Author(s): Takahiro Sawada, Xuefeng Jing, Masayasu Miyajima, Emi Shimada and Kazushige Sakaguchi
  • Organizer: Eph/ephrins and cancer meeting
  • Place of Presentation: Washington-Salem, NC, USA
  • Year and Date: 2010-06-22
• [Presentation] Functional and structural analysis of Eph-FGFR and Eph-GHR interactions (oral presentation) (2010)
  • Author(s): Kazushige Sakaguchi, Takahiro Sawada,Xuefeng Jing, Emiko Shimada, and Masayasu Miyajima
  • Organizer: Eph/ephrins and cancer meeting
  • Place of Presentation: Washington-Salem, NC, USA
  • Year and Date: 2010-06-22