Androgen-regulated ECM remodeling during sexual differentiation of external genitalia
Project/Area Number |
18K06837
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 48010:Anatomy-related
|
Research Institution | Wakayama Medical University |
Principal Investigator |
Suzuki Kentaro 和歌山県立医科大学, 先端医学研究所, 准教授 (20404345)
|
Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
Keywords | アンドロゲン / 性差 / 細胞外マトリックス / MMP / 外生殖器 / 細胞外マトリクス / Mmp / sexome / SEXOME / ECM / 器官形成 / 性差形成 / 間葉 |
Outline of Final Research Achievements |
Androgen is a master regulator to induce sexual differences between male and female. This study identified androgen-regulated Mmp (matrix metalloproteinase) is required for establishment of external genital sex differences. This Mmp was expressed dominantly in male genital tubercle (GT), an anlage of external genitalia, and its substrate also showed male-biased expression during sex differentiation of external genitalia. Inhibitory experiment by using tissue organotypic slice culture system showed that this Mmp lead to ECM remodeling in GT mesenchyme and it was required for male-biased mesenchymal cell migration. Furthermore, its expression was regulated in a androgen-AP1 dependent manner.
|
Academic Significance and Societal Importance of the Research Achievements |
アンドロゲンが性差形成に不可欠であることは自明である。しかし、どのような遺伝子を介してどうやって性差を形成しているのか、アンドロゲンによる性差形成機構の解明には至っていない。 これまで報告してきた細胞増殖の性差、細胞骨格の性差、細胞挙動の性差に加え、本研究からECMリモデリングがアンドロゲンによる性差形成に必要な新たなプロセスであることを明らかにした。今回同定したMmpは、外生殖器以外の器官においても発現しており、様々ながんで高発現していることが報告されている。本研究から得られた知見は、外生殖器の性差形成のみならず病態の性差形成機構を理解する上でも有用な知見である。
|
Report
(4 results)
Research Products
(20 results)
-
[Journal Article] Sexual fate of murine external genitalia development: conserved transcriptional competency for male-biased genes in both sexes.2021
Author(s)
Kajioka D, Suzuki K, Matsushita S, Hino S, Sato T, Takada S, Isono K, Takeo T, Kajimoto M, Nakagata N, Nakao M, Suyama M, DeFalco T, Miyagawa S, Yamada G.
-
Journal Title
Proc Natl Acad Sci U S A.
Volume: in press
Related Report
Peer Reviewed
-
-
[Journal Article] Dynamic erectile responses of a novel penile organ model utilizing TPEM.2021
Author(s)
Hashimoto D, Hirashima T, Yamamura H, Kataoka T, Fujimoto K, Hyuga T, Yoshiki A, Kimura K, Kuroki S, Tachibana M, Suzuki K, Yamamoto N, Morioka S, Sasaki T, Yamada G.
-
Journal Title
Biol Reprod.
Volume: in press
Issue: 4
Pages: 875-886
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
[Journal Article] Mesenchymal actomyosin contractility is required for androgen-driven urethral masculinization in mice.2019
Author(s)
Acebedo AR, Suzuki K, Hino S, Alcantara MC, Sato Y, Haga H, Matsumoto KI, Nakao M, Shimamura K, Takeo T, Nakagata N, Miyagawa S, Nishinakamura R, Adelstein RS, Yamada G.
-
Journal Title
Commun. Biol.
Volume: eCollection
Issue: 1
Pages: 95-95
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
[Journal Article] Single Nucleotide Polymorphisms of HAAO and IRX6 Genes as Risk Factors for Hypospadias.2019
Author(s)
Kojima Y, Koguchi T, Mizuno K, Sato Y, Hoshi S, Hata J, Nishio H, Hashimoto D, Matsushita S, Suzuki K, Miyagawa S, Hui CC, Tanikawa C, Murakami Y, Yamada G, Hayashi Y, Matsuda K.
-
Journal Title
J Urol.
Volume: 201(2)
Issue: 2
Pages: 386-392
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-