The elucidation of interaction between glomerular podocyte and endothelium in glomerular injury

• Project/Area Number: 24591187
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Tohoku University
• Principal Investigator: KIYOMOTO hideyasu 東北大学, 東北メディカル・メガバンク機構, 教授 (00304585)
• Co-Investigator(Kenkyū-buntansha): MORIWAKI Kumiko 香川大学, 医学部, 助教 (90398040)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 糸球体腎炎 / 血栓性微小血管炎 / ポドサイト / 内皮障害 / PAI－1阻害薬 / PAI-1 / MCP-1 / LRP / マクロファージ / mRNA / クロピドグレル / 慢性糸球体腎炎 / PAI-1阻害薬 / 内皮細胞 / ＶＥＧＦ / ＥＲ４Ｇ / 抗Thy1.1腎炎 / VEGF / ER4G

Outline of Final Research Achievements

The loss of interaction between glomerular podocyte and endothelium leads to severe glomerular injuries such as thrombotic micro-angiopathy (TMA) like glomerulonephritis. Both cells affect each other with endocrine and/or paracrine manner beside the glomerulus basement membrane. The lack of cross-talk between cells leads to initiate glomerulonephritis and accelerate the disease condition. There are certain activities of the plasminogen activation inhibitor (PAI-1) around the glomerular podocyte area in clinical thrombi-genesis and inflammatory reaction, which may involve the progression glomerular damages such as TMA. We verified a newly developing PAI-1 inhibitor to examine the effectiveness onto the animal models of glomerulonephritis. The inhibitor of PAI-1 significantly decreased inflammatory changes and ameliorates the progression of renal injury. These findings suggest a small molecule PAI-1 inhibitor represents new therapeutic strategy as anti-inflammatory agents.

Research Products

• [Journal Article] Plasticity of renal erythropoietin-producing cells governs fibrosis (2013)
  • Author(s): Souma T, Yamazaki S, Moriguchi T, Suzuki N, Hirano I, Pan X, Minegishi N, Abe M, Kiyomoto H, Ito S, Yamamoto M
  • Journal Title: J Am Soc Nephrol Volume: 24 Issue: 10 Pages: 1599-1616
  • DOI: 10.1681/asn.2013010030
  • Peer Reviewed / Open Access
• [Journal Article] A small molecule inhibitor to plasminogen activator inhibitor 1 inhibits macrophage migration. (2013)
  • Author(s): Ichimura A1, Matsumoto S, Suzuki S, Dan T, Yamaki S, Sato Y, Kiyomoto H, Ishii N, Okada K, Matsuo O, Hou FF, Vaughan DE, van Ypersele de Strihou C, Miyata T.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 33(5) Pages: 935-942
  • Peer Reviewed
• [Journal Article] Beneficial role of tolvaptan in the control of body fluids without reductions in residual renal function in patients undergoing peritoneal dialysis. (2013)
  • Author(s): Mori T, Oba I, Koizumi K, Kodama M, Shimanuki M, Tanno M, Chida M, Saito M, Kiyomoto H, Miyazaki M, Ogawa S, Sato H, Ito S.
  • Journal Title: Adv Perit Dial Volume: 29 Pages: 33-37
  • Peer Reviewed
• [Journal Article] A rare case among hypertensive patients: how do we handle reninomas? (2013)
  • Author(s): Okuda H, Abe M, Kiyomoto H.
  • Journal Title: Intern Med Volume: 52(17) Pages: 1853-1853
  • NAID: 130003365800
• [Presentation] Pharmacological inhibition of plasminogen activator inhibitor (PAI)-1 ameliorates glomerular podocyte injury in anti-Thy1.1 glomerulonephritis. (2012)
  • Author(s): Hideyasu Kiyomoto, MD, PhD, Kumiko Moriwaki, MD, PhD, et al.
  • Organizer: American Society of Nephrology 2012
  • Place of Presentation: San Diego, California,USA