| Project/Area Number |
24591370
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Endocrinology
|
|---|
| Research Institution | Wakayama Medical University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAWADA Takahiro 和歌山県立医科大学, 先端医学研究所, 非常勤講師 (00382325)
FURUSHIMA Kenryo 和歌山県立医科大学, 先端医学研究所, 講師 (50392105)
JING Xuefeng 和歌山県立医科大学, 先端医学研究所, 講師 (70316123)
MIYAJIMA Masayasu 和歌山県立医科大学, 共同利用施設, 講師 (80137257)
ARAI Daiki 和歌山県立医科大学, 先端医学研究所, 学内助教 (90725574)
MIWA Hideto 和歌山県立医科大学, 医学部, 准教授 (50231626)
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | 体格決定 / 成長ホルモン / インスリン様成長因子 / Eph / ephrin / JAK2 / STAT / シグナル伝達 / GH-IGF1 axis / EphA4 / IGF1 / 体格 |
|---|
| Outline of Final Research Achievements |
The growth hormone (GH)-insulin-like growth factor 1 (IGF1) axis mediates postnatal body growth. The GH receptor has been regarded as the sole receptor that mediates the JAK2/STAT5B signal toward IGF1 synthesis. Here, we report a signaling pathway that regulates postnatal body growth through EphA4, a member of the Eph family of receptor tyrosine kinases and a mediator of the cell-cell contact-mediated signaling. EphA4 forms a complex with the GH receptor, JAK2, and STAT5B and enhances Igf1 expression predominantly via the JAK2-dependent pathway, with some direct effect on STAT5B. Mice with a defective Epha4 gene have a gene dose-dependent short stature and low plasma IGF1 levels. Pituitary Gh mRNA and plasma GH levels were not reduced. IGF1 injection rescued the phenotype of Epha4-KO mice. These findings suggest that the local cell-cell contact-mediated ephrin/EphA4 signal is as important as the humoral GH signal in IGF1 synthesis and body size determination.
|
