Project/Area Number |
18K06938
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 48040:Medical biochemistry-related
|
Research Institution | Wakayama Medical University |
Principal Investigator |
Gen Yamada 和歌山県立医科大学, 先端医学研究所, 教授 (80174712)
|
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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 海綿体 / 男性ホルモン / シヌソイド / 勃起 / 平滑筋 / 二光子顕微鏡 / 培養系 / ストレス応答 / 血管形成 / 生殖器 / 間葉細胞 / 雄性化 / 男性ホルモンレセプター(AR) / VEGF / 男性ホルモンレセプター(AR) / ED |
Outline of Final Research Achievements |
In the upper (dorsal) part of penis, corpus cavernosum (CC) plays fundamental roles for erection. The basis of ED by penile abnormality is poorly understood. To analyze the 3D structure of murine CC sinusoid, 3D reconstruction was performed. Sinusoids prominently developed adjacent to tunica albuginea. As for pathogenic signaling, aged samples contained ectopic chondrocytes and the expression of SOX9, chondrogenic regulator, was upregulated and the expression of RBPJ, the Notch signal regulator, was downregulated. Furthermore, a novel in vitro explant system to analyze the dynamic erectile contraction/relaxation was established. The data show regulatory contraction/relaxation processes by phenylephrine (PE) and nitric oxide (NO) donor. Two photon excitation microscopy (TPEM) observation shows the synchronous movement of sinusoidal space and the CC. The model enables to directly analyze various stressed conditions.
|
Academic Significance and Societal Importance of the Research Achievements |
勃起不全(ED)は、高齢化から増加している。海綿体の研究は、生理学的実験等が主体であり、その構造と動態に関する研究は希少であった。本研究ではマウスexplant(組織片)による新規な培養を行い、海綿体発生や機能に関する制御因子群の解明、男性ホルモン系との関連を解明した。その結果PEやSNPによる収縮/弛緩反応の誘導が可能となり、バイアグラなどの薬剤添加により弛緩機能の変化を直接評価することができた。これらはシヌソイドを含む、微細で高度な血管系を基盤とする疾患の理解に有用と考えられる。
|