Vicious cycle toward glomerulosclerosis

• Project/Area Number: 26461210
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: University of Tsukuba
• Principal Investigator: Nagata Michio 筑波大学, 医学医療系, 教授 (10192238)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ポドサイト / 糸球体硬化 / インテグリン / PAI-1 / 過酸化脂質 / 泡沫細胞 / 腎臓 / 細胞剥離 / 内皮細胞 / エンドサイトーシス / クロストーク

Outline of Final Research Achievements

Podocyte specific CD25 expression mice causes glomerular injury by inje3ction of its ligand immunotoxin. We found that podocyte loss caused intracapillary PAI-1 up-regulation from endothelial cells that subsequently bound with uPA leading to beta-1 integrain endocytosis. In addition endothelial adhesion molecules up-regulation is accompanied by lipid peroxidation and foam cell formation. All together may be responsible for focal segmental gloemrulosclerosis.

Research Products

• [Int'l Joint Research] National Institute of Health(米国)
• [Journal Article] Podcyte injury and its consequences. (2016)
  • Author(s): Nagata M
  • Journal Title: Kidney International Volume: 89 Issue: 6 Pages: 1221-30
  • DOI: 10.1016/j.kint.2016.01.012
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Heparan sulfate 6-O-endosulfatases, Sulf1 and Sulf2, regulate glomerular integrity by modulating growth factor signaling. (2016)
  • Author(s): Takashima Y, Keino-Masu K, Yashiro H, Hara S, Suzuki T, van Kuppevelt TH, Masu M, Nagata M
  • Journal Title: Am J Physiol Renal Physiol. Volume: 310 Issue: 5 Pages: 395-408
  • DOI: 10.1152/ajprenal.00445.2015
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Podocyte injury-driven lipid peroxidation accelerates the infiltration of glomerular foam cells in focal segmental glomerulosclerosis. (2015)
  • Author(s): Hara S, Kobayashi N, Sakamoto K, Ueno T, Manabe S, Takashima Y, Hamada J, Pastan I, Fukamizu A, Matsusaka T, Nagata M.
  • Journal Title: Am J Pathol Volume: 185 Issue: 8 Pages: 2118-31
  • DOI: 10.1016/j.ajpath.2015.04.007
  • Peer Reviewed / Open Access / 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 Volume: 308 Issue: 1 Pages: F98-F104
  • DOI: 10.1152/ajprenal.00228.2013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ポドサイトと内皮細胞のクロストーク. (2015)
  • Author(s): 小林 凡子 長田 道夫
  • Journal Title: 腎と透析 Volume: 78 Pages: 390-394
• [Presentation] Glomerular microcirculation in renal disease: Adaptive response or start of glomerular dysfunction? (2017)
  • Author(s): Michio Nagata
  • Organizer: 3rdInternational Renal Pathology Conference
  • Place of Presentation: New Delhi, India
  • Year and Date: 2017-02-10
  • Int'l Joint Research / Invited
• [Presentation] 糸球体濾過障壁の恒常性破綻とFSGS (2016)
  • Author(s): 長田道夫
  • Organizer: 第110回 腎生理集団会
  • Place of Presentation: コングレスクエア日本橋（東京都中央区）
  • Year and Date: 2016-09-10
  • Invited
• [Presentation] Pathophysiology podocyte disease (2015)
  • Author(s): Michio Nagata
  • Organizer: 2nd International of Renal Pahtology
  • Place of Presentation: Tsukuba
  • Year and Date: 2015-03-04 – 2015-03-07
  • Invited
• [Presentation] Primary podocyte injury-caused in situ thrombotic microangiopathy promotes extra podocyte damage by PAI-1/uPA/uPAR complex mediated beta1-integrin endocytosis. (2014)
  • Author(s): Namiko Kobayashi, Toshiharu Ueno1, Kumi Ohashi1, Satoshi Hara1, Kazuo Sakamoto, Shun Manabe,Yasutoshi Takashima, Taiji Matsusaka, Toshio Miyata, Michio Nagata.
  • Organizer: American Society of Nephrology Kidney Week
  • Place of Presentation: Philadelphia,
  • Year and Date: 2014-11-08
• [Presentation] Podocyte injury-driven endocapillary PAI-1 promotes a vicious cycle of podocyte lossviabeta-1 integrin endocytosis. (2014)
  • Author(s): Namiko Kobayashi, Toshiharu Ueno, Satoshi Hara, Shun Manabe, Yukina Takahashi, Kazuo Sakamoto, Tomo Suzuki, Yasutoshi Takashima, Taiji Matsusaka, Toshio Miyata, Michio Nagata.
  • Organizer: American Society of Nephrology Kidney Week
  • Place of Presentation: Tokyo
  • Year and Date: 2014-05-15
• [Book] 腎と透析 (2017)
  • Author(s): 長田 道夫
  • Total Pages: 8
  • Publisher: 東京医学社