Functional analysis of nephrotic syndrome caused by TRPC6 gene mutation and new drug development

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16262
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Kobe University
• Principal Investigator: Nakanishi Keita 神戸大学, 医学研究科, 特命助教 (00793712)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 遺伝性ネフローゼ症候群 / TRPC6

Outline of Final Research Achievements

We analyzed Japanese patients diagnosed with steroid resistant nephrotic syndrome by next generation sequencer and detected some kinds of gene defects which were reported as the causative genes of nephrotic syndrome.
For analysis of TRPC6 mutations, Ca influx was performed by transfected the cTRCP6 into human-derived cells. It was confirmed that the increase of intracellular Ca concentration was suppressed with Larixyl Acetate. In the future, we plan to transfect cTRPC6 containing mutations into human-derived cells, and to confirm whether changes in Ca concentration are observed by the introduction of mutations.

Free Research Field

小児科

Academic Significance and Societal Importance of the Research Achievements

ステロイド抵抗性ネフローゼ症候群に対する次世代シークエンサーを用いた解析結果から、日本における遺伝性ネフローゼ症候群の割合を明らかにすることができた。遺伝性ネフローゼ症候群の中には特別な治療によって腎予後を改善できる遺伝子も含まれており、診断する意義が高いと考えられた。
TRPC6に対する機能解析については、正常のTRPC6遺伝子導入を行ったヒト由来細胞でCa influxを行った結果、Larixyl Acetateによって細胞内Ca濃度上昇が抑制された。Larixyl AcetateがTRPC6遺伝子異常例に対する新薬となる可能性が考えられた。