Elucidation of subcellular signals in mesangial proliferative glomerular nephritis

• Project/Area Number: 25461617
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: The University of Tokyo
• Principal Investigator: TSURUMI HARUKO 東京大学, 医学部附属病院, 登録研究員 (20632269)
• Co-Investigator(Kenkyū-buntansha): HARITA YUTAKA 東京大学, 医学部附属病院, 講師 (10451866) ; HATTORI MOTOSHI 東京女子医科大学, 医学部, 教授 (50192274) ; KURIHARA HIDETAKE 順天堂大学, 医学部, 准教授 (80311976)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 小児腎・泌尿器学 / 病理学 / 細胞・組織 / シグナル伝達 / 細胞骨格タンパク質 / 糸球体腎炎 / 接着斑タンパク質 / 細胞極性 / 細胞運動 / メサンギウム細胞 / 腎炎 / 腎臓 / 細胞骨格 / 細胞接着

Outline of Final Research Achievements

We examined precise localization of F-actin binding protein EPLIN and intercellular junction protein Afadin in mesangial cells in vivo and in vitro and found alteration of expression and localization of these cytoskeletal regulators underlies phenotypical change of mesangial cells induced by mitogens (Tsurumi H. et al. Kidney Int. 2014, Tsurumi H. et al. Lab Invest. 2016). Comprehensive investigation of spatiotemporal dynamics of mesangial intercellular molecules is warranted to elucidate precise mechanisms of mesangial proliferative glomerulonephritis.

Research Products

• [Journal Article] Afadin is localized at cell-cell contacts of mesangial cells and regulates migratory polarity. (2016)
  • Author(s): Tsurumi H, Kurihara H, Miura K, Ohta Y, Igarashi T, Oka A, Horita S, Hattori M, Harita Y
  • Journal Title: Lab Invest Volume: 96 Issue: 1 Pages: 49-59
  • DOI: 10.1038/labinvest.2015.133
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Afadin regulates RhoA/Rho-associated protein kinase signaling to control formation of actin stress fibers in kidney podocytes. (2015)
  • Author(s): Saito K,Shiino T,Kurihara H,Harita Y,Hattori S, Ohta Y
  • Journal Title: Cytoskeleton Volume: 72 Issue: 3 Pages: 146-156
  • DOI: 10.1002/cm.21211
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] SPECT/CT to diagnose pleuroperitoneal communication-associated hydrothorax in peritoneal dialysis. (2015)
  • Author(s): Nishiyama K, Fukushima K, Jo T, Miyai T, Kanda S, Sugawara N, Ishizuka K, Chikamoto H, Akioka Y, Hattori M.
  • Journal Title: Kidney Int. Volume: 87 Pages: 866-866
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1 accelerates podocyte loss via uPAR-mediated β1-integrin endocytosis. (2015)
  • Author(s): Kobayashi N, Ueno T, Ohashi K, Yamashita H, Takahashi Y, Sakamoto K, Manabe S, Hara S, Takashima Y, Dan T, Pastan I, Miyata T, Kurihara H, Matsusaka T, Reiser J, Nagata M.
  • Journal Title: Am J Physiol Renal Physiol Volume: 308・6 Issue: 6 Pages: F614-F626
  • DOI: 10.1152/ajprenal.00616.2014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Epithelial protein lost in neoplasm modulates platelet-derived growth factor-mediated adhesion and motility of mesangial cells (2014)
  • Author(s): Haruko Tsurumi, et. al
  • Journal Title: Kidney International Volume: Epub Issue: 3 Pages: 548-557
  • DOI: 10.1038/ki.2014.85
  • Peer Reviewed / Open Access
• [Journal Article] aPKCλ maintains the integrity of the glomerular slit diaphragm through trafficking of nephrin to the cell surface. (2014)
  • Author(s): Satoh D, Hirose T, Harita Y, Daimon C, Harada T, Kurihara H, Yamashita A, Ohno S.
  • Journal Title: J Biochem. Volume: 156(2) Issue: 2 Pages: 115-28
  • DOI: 10.1093/jb/mvu022
  • Peer Reviewed / Open Access
• [Journal Article] Decreased glomerular filtration as the primary factor of elevated circulating suPAR levels in focal segmental glomerulosclerosis. (2014)
  • Author(s): Harita Y, Ishizuka K, Tanego A, Sugawara N, Chikamoto H, Akioka Y, Tsurumi H, Miura K, Gotoh Y, Tsujita M, Yamamoto T, Horike K, Takeda A, Oka A, Igarashi T, Hattori M.
  • Journal Title: Pediatr Nephrol. Volume: 29 Issue: 9 Pages: 1553-1560
  • DOI: 10.1007/s00467-014-2808-5
  • Peer Reviewed
• [Journal Article] LMX1B Mutation with Residual Transcriptional Activity as a Cause of Isolated Glomerulopathy. (2014)
  • Author(s): Isojima T, Harita Y, Furuyama M, Sugawara N, Ishizuka K, Horita S, Kajiho Y, Miura K, Igarashi T, Hattori M, Kitanaka S
  • Journal Title: Nephrol Dial Transplant Volume: 29 Issue: 1 Pages: 81-8
  • DOI: 10.1093/ndt/gft359
  • Peer Reviewed
• [Journal Article] Laminin alpha1 regulates age-related mesangial cell proliferation and mesangial matrix accumulation through the TGFbeta pathway. (2014)
  • Author(s): Ning L, Kurihara H, de Vega S, Ichikawa-Tomikawa N, Xu Z, Nonaka R, Yamada Y, Miner JH, Arikawa-Hirasawa E
  • Journal Title: Am J Pathol Volume: 184 Issue: 6 Pages: 1683-1694
  • DOI: 10.1016/j.ajpath.2014.02.006
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] メサンギウム細胞接着構造は極性形成に必要であり細胞運動を制御する (2015)
  • Author(s): 鶴見晴子、栗原秀剛、三浦健一郎、張田豊
  • Organizer: 日本小児腎臓病学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-06-26
• [Presentation] 細胞間蛋白質Afadinはメサンギウム細胞の極性を維持し細胞運動性を制御する (2015)
  • Author(s): 鶴見晴子、栗原秀剛、三浦健一郎、服部元史、張田豊
  • Organizer: 日本腎臓病学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-06-05
• [Presentation] Alteration of mesangial cell-cell junction in glomerulonephritis is associated with directional migration (2015)
  • Author(s): Haruko T, Yutaka H, Hidetake K, Kenichiro M, Motoshi H, Akira O
  • Organizer: Asian Society for Pediatric Reseach
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-15 – 2015-04-17
• [Presentation] Alteration of mesangial cell-cell junction in glomerulonephritis is associated with directional migration (2015)
  • Author(s): Haruko T, Yutaka H, Tidetake K, Kenichiro M, Motoshi H, Akira O
  • Organizer: Asian Society for Paediatric Research
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-15
• [Presentation] 蛋白尿の分子生理学 (2015)
  • Author(s): 張田豊
  • Organizer: 近畿小児腎臓病研究会
  • Place of Presentation: 大阪
  • Year and Date: 2015-03-28
  • Invited
• [Presentation] ネフローゼ症候群の遺伝子解析 (2014)
  • Author(s): 張田豊
  • Organizer: 第53回遺伝子医学研究会
  • Place of Presentation: 新宿
  • Year and Date: 2014-07-25
  • Invited
• [Presentation] 蛋白尿の成因 (2014)
  • Author(s): 張田豊
  • Organizer: 日本腎臓病学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] 後天性ネフローゼ症候群再発時におけるスリット膜構成分子の細胞内局在変化の検討 (2014)
  • Author(s): 石塚喜世伸、張田豊、梶保祐子、鶴見晴子、浅野達雄、西山慶、菅原典子、久野正貴、近本裕子、秋岡祐子、山口裕、服部元史
  • Organizer: 日本小児腎臓病学会
  • Place of Presentation: 秋田
  • Year and Date: 2014-06-05 – 2014-06-07
• [Presentation] Coordinated actin remodeling of mesangial cells by epithelial protein lost in neoplasm (EPLIN) in mesangial proliferative glomerulonephritis. (2014)
  • Author(s): Tsurumi H, Harita Y, Kurihara H, Miura K, Hattori M, Oka A, Igarashi T.
  • Organizer: Pediatric Academic Societies and Asian Society for Pediatric Research Joint Meeting
  • Place of Presentation: Vancouver, Canada
• [Presentation] EPLIN(Epithelial protein lost in neoplasm)は接着斑を安定化し、PDGF刺激によるメサンギウム細胞の運動性を制御する (2013)
  • Author(s): 鶴見 晴子, 張田 豊, 栗原 秀剛 , 林 健二, 小迫 英尊, 服部 元史, 服部 成介, 岡 明, 五十嵐 隆
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸