Role of Gpr116 in maintenance of the glomerular filtration barrier in mice

• Project/Area Number: 16K07344
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: Nakamura Nobuhiro 東京工業大学, 生命理工学院, 准教授 (80361765)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 受容体 / 血管内皮細胞 / 腎蔵 / シグナル伝達 / 糸球体 / 細胞内情報伝達 / ノックアウトマウス / 血管内皮 / 細胞・組織

Outline of Final Research Achievements

In this study, 1) we showed that Gpr116 is localized to the glomerular endothelial cells by immunoelectron microscopy. 2) We identified genes of which expression are altered in the glomerular endothelial cells of Gpr116-deficient mice. 3) We identified candidates of downstream signaling molecules, which are activated by Gpr116 overexpression. 4) We observed that several intracellular signaling pathways were activated to a lesser extent in Gpr116 overexpressing cells by shear stress.

Academic Significance and Societal Importance of the Research Achievements

腎炎や腎不全に有効な治療法が確立しておらず，年々透析患者数が増加する傾向にあって患者の医療費負担や国の財政圧迫が国内外問わず問題視されている。その為，糸球体濾過障壁の形成維持機構の解明が急務となっている。本研究は，糸球体血管内皮における情報伝達とその作用という新しい切り口から 濾過障壁の恒常性維持機構の解明に挑戦する点が特色であり，今まで不明な点が多かった糸球体内皮細胞の特性を明らかにするばかりでなく，腎疾患の病態の基礎・臨床研究の進展に貢献できる点で意義深い。

Research Products

• [Int'l Joint Research] Gadjah Mada University(インドネシア)
• [Journal Article] Loss of the adhesion G-protein coupled receptor ADGRF5 in mice induces airway inflammation and the expression of CCL2 in lung endothelial cells (2019)
  • Author(s): Kubo F, Ariestanti DM, Oki S, Fukuzawa T, Demizu R, Sato T, Sabirin RM, Hirose S, Nakamura N
  • Journal Title: Respiratory Research Volume: 20 Issue: 1 Pages: 11-11
  • DOI: 10.1186/s12931-019-0973-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] USP19-mediated deubiquitination facilitates the stabilization of HRD1 ubiquitin ligase. (2016)
  • Author(s): Harada K, Kato M, Nakamura N
  • Journal Title: Int. J. Mol. Sci. Volume: 17 Issue: 11 Pages: 1829-1829
  • DOI: 10.3390/ijms17111829
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Gタンパク質共役型受容体ADGRF5の欠損は肺血管内皮細胞における炎症性分子の発現と喘息に似た表現型を誘導する (2018)
  • Author(s): 久保 文雅、Donna Ariestanti、沖 颯太、福澤拓、出水 遼太郎、佐藤朋哉、Rahmaningsih Sabirin、広瀬茂久、中村 信大
  • Organizer: 第91回日本生化学会大会
• [Presentation] Intracellular signaling Mechanism of G-protein coupled receptor ADGRF5 (2018)
  • Author(s): 佐藤朋哉、加藤真子、久保 文雅、中村 信大
  • Organizer: 13th Toin International Symposium on Biomedical Engineering
  • Int'l Joint Research
• [Presentation] Adgrf5欠損マウスは気管支喘息および肺線維症様の表現型を現す (2017)
  • Author(s): 久保 文雅、Donna Ariestanti、沖 颯太、Rahmaningsih Sabirin、出水 遼太郎、中村 信大
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] Adgrf5 deficient mice exhibit bronchial asthma- and fibrosis-like phenotypes (2017)
  • Author(s): Fumimasa Kubo, Donna Maretta Ariestanti, Souta Oki, Rahmaningsih Mara Sabirin, Ryota Demizu, and Nobuhiro Nakamura
  • Organizer: 12th Toin International Symposium on Biomedical Engineering
  • Int'l Joint Research
• [Presentation] FNDC4 Promotes Brown-Like Adipocyte Formation and Glucose Clearance via an Orphan G-protein Coupled Receptor (2017)
  • Author(s): Xiaochuan Ma, Madeleen Bosma, Olga Shilkova, Maude Giroud, Juan C Higareda-Almaraz, Venetia Bazioti, Tilo Wuensch, Malin Elven, Steven Seaman, Olli Ritvos, Nobuhiro Nakamura, Shigehisa Hirose, Martin Irmler, Johannes Beckers, Robert Janowski, Dierk Niessing, Brad ST Croix, Tarja Niemi, Markku Taittonen, 他８名
  • Organizer: American Diabetes Association
  • Int'l Joint Research
• [Remarks]
  • URL: http://www.nnakamura.bio.titech.ac.jp/TOP.html
• [Remarks]
  • URL: http://www.nnakamura.bio.titech.ac.jp/research.html