2018 Fiscal Year Final Research Report
The mechanism for proximal tubular cyst formation by PC1 trafficking problem associated with ER dysfunction providing drug targets.
| Project/Area Number |
15K09302
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Meiji Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Keywords | 多発性嚢胞腎 / 水チャネル / アデノシン / 増殖因子 / 近位尿細管 / 治療薬ターゲット / REG1 / AQP11 |
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| Outline of Final Research Achievements |
The activity of cAMP was increased in AQP11 null kidney developing proxmal-tubular-selective cysts, which is similar to the results of collecting-duct-type polycystic kidneys. Among four types of adenosine receptors (A1, A2A, A2B and A3),only A3 was enhanced. Mass spectroscopic analysis of the kidney proteins from two-week old AQP11 null mice initiating the cyst formation had 1.5 times more enhanced expression of 162 proteins than wild mice, including connective tissue-related proteins, angiotensinogen and, above all, Reg1 (Lithostathine),a growth factor for the pancreas with ten times increase. The decreased proteins by less than 0.8 times included mitochondria-related proteins.
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| Free Research Field |
水電解代謝疾患、腎臓内科
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| Academic Significance and Societal Importance of the Research Achievements |
多発性嚢胞腎は透析導入原因疾患の2-3％を占める優性遺伝の腎疾患であり、その発症と進行の機序解明は、より有効な治療のターゲット分子を明らかにして、新たな薬剤の開発の端緒となりうる。唯一の治療薬トルバプタンは遠位尿細管にしか作用せず、近位尿細管に有効な薬剤の開発が求められている。今回研究対象にしたAQP11欠損マウスは近位尿細管にしか嚢胞ができない多発性嚢胞腎モデルであり、この目的に合致した数少ないモデルの一つである。今回の研究で、これまで全く検討されていなかったアデノシン３型受容体とReg1の関与が示唆された意義は大きい。今後ヒトの多発性嚢胞腎でも検討して、治療薬開発が望まれる。
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