Mechanism of renal cyst formation induced by abnormal signaling through basal body

• Project/Area Number: 18K15983
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: MATSUO KAZUHIKO 京都府立医科大学, 医学(系)研究科(研究院), 助教 (70599753)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 中心小体 / 一次繊毛 / kendrin / 一次線毛 / 中心体 / 嚢胞腎

Outline of Final Research Achievements

The molecular mechanism of renal cyst formation induced by abnormalities in primary cilia is unknown. This study was conducted to elucidate the molecular mechanism by which cystic kidneys are formed by suppression of gene expression of kendrin, which is localized at the base of primary cilia (outside of primary cilia). The applicant has clarified the interaction of kendrin with proteins localized to INV-C in the primary cilia. Analysis of kendrin interaction proteins identified a novel ciliary protein. Furthermore, we found that genetic disruption of kendrin causes abnormal localization of the protein in the primary cilia.

Academic Significance and Societal Importance of the Research Achievements

本研究より、一次繊毛外（基底小体）に局在するkendrinが、一次線毛内のタンパク質の局在に寄与することで一次繊毛を介したシグナル伝達を調整している可能性が強く示唆される結果を得た。これは、嚢胞腎形成メカニズム解明へのマイルストーンとして意義深いと考えられる。悪化した腎機能を回復させることは困難であるが、本研究の成果をもとに嚢胞腎形成のメカニズム解明が進めば、病態の進行を防ぎ腎機能を悪化させない予防薬の開発や、新規治療薬の開発の一助となる事が期待できる。

Research Products

• [Journal Article] Raman Spectroscopic Assessment of Myocardial Viability in Langendorff-Perfused Ischemic Rat Hearts (2021)
  • Author(s): Koki Ikemoto, Kosuke Hashimoto, Yoshinori Harada, Yasuaki Kumamoto, Michiyo Hayakawa, Kentaro Mochizuki, Kazuhiko Matsuo, Kenta Yashiro, Hitoshi Yaku, Tetsuro Takamatsu, Hideo Tanaka
  • Journal Title: ACTA HISTOCHEMICA ET CYTOCHEMICA Volume: 54 Issue: 2 Pages: 65-72
  • DOI: 10.1267/ahc.21-00016
  • NAID: 130008031022
  • ISSN: 0044-5991, 1347-5800
  • Year and Date: 2021-04-28
  • Peer Reviewed / Open Access
• [Journal Article] Bioconjugation strategy for cell surface labelling with gold nanostructures designed for highly localized pH measurement. (2018)
  • Author(s): Leonardo Puppulin, Shigekuni Hosogi, Hongxin Sun, Kazuhiko Matsuo, Toshio Inui, Yasuaki Kumamoto, Toshinobu Suzaki, Hideo Tanaka and Yoshinori Marunaka
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 5278-5278
  • DOI: 10.1038/s41467-018-07726-5
  • NAID: 120006549200
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 一次繊毛タンパク質CEP290/NPHP6は微小管系を介して細胞接着を制御する。 (2021)
  • Author(s): 松尾和彦 八代健太
  • Organizer: 第44回日本分子生物学会年会
• [Presentation] 一次繊毛タンパク質CEP290/NPHP6は、細胞運動と接着を制御する (2018)
  • Author(s): 松尾和彦 八代健太
  • Organizer: 日本解剖学会