The role of non-G protein coupled receptor related signal transduction in the pathology of polycystic kidney disease

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16278
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Wakayama Medical University
• Principal Investigator: Hama Taketsugu 和歌山県立医科大学, 医学部, 助教 (00508020)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: TRIP13 / AGS7 / アクセサリータンパク / 多発性嚢胞腎 / GPCR / Gβγ

Outline of Final Research Achievements

Gα and Gβγ are dissociated from G protein. These two molecules are involved in signal transduction. In polycystic kidney disease (PKD), there are many reports that Gα and G protein coupled receptor (GPCR) are involved in the pathopysiology, whereas, there are few about Gβγ through non-GPCR. TRIP13, binding protein with Gβγ, is recentlry focused. In this study, we detected that TRIP13 bound with Gβγ were less in the kidney of PKD than in normal. Non-GPCR signal transduction may also be involved in the pathopysiology of PKD.

Free Research Field

腎臓病

Academic Significance and Societal Importance of the Research Achievements

多発性嚢胞腎(PKD)は、常染色体優性遺伝型(ADPKD)と常染色体劣性遺伝型(ARPKD)とがある。ともに腎不全や高血圧、多くの合併症があり、その早期診断や治療の重要性が認識されている。PKDの研究には、GαおよびGタンパク受容体(GPCR)に注目したものが多く、トルバプタンなどGPCR受容体阻害薬がPKDの治療として開発されてきた。しかし、GタンパクはGαとGβγに分かれ、Gβγもシグナル伝達に関与することが分かっている。これまでのGPCRに依存しないGβγとGPCR非依存性のシグナル伝達の役割が判明すれば、PKDの新たな治療を開く可能性がある。