Elucidation of the mechanism of impaired endocytosis to develop new treatment options for Dent's disease

2017 Fiscal Year Final Research Report

• Project/Area Number: 16H06750
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Satoh Nobuhiko 東京大学, 医学部附属病院, 助教 (80572552)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Keywords: Dent病 / CLC5 / エンドサイトーシス

Outline of Final Research Achievements

We examined the readthrough effect of PTC124(ataluren) on nonsense mutation of CLCN5, the causative gene of Dent's disease with impaired endocytosis in renal proximal tubules. Further, we examined the relationship between the functional coupling of CLC5/V-ATPase and defective endocytosis. In HEK293 cells, a certain read-through effect on nonsense mutation R704X, which is commonly reported both domestically and abroad, was observed, suggesting that PTC 124 was effective for Dent's disease caused by nonsense mutations. Intracellular pH measurement in mouse renal proximal tubules revealed that insulin activates V-ATPase via PI3K / Akt pathway.

Free Research Field

腎生理学