The role of CTGF in peritoneal lymphangiogenesis

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H06746
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Aichi Medical University
• Principal Investigator: Kinashi Hiroshi 愛知医科大学, 医学部, 講師 (70805275)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: 腹膜透析 / 腹膜線維症 / リンパ管新生 / CTGF / VEGF-C

Outline of Final Research Achievements

Lymphangiogenesis in peritoneal fibrosis may cause ultrafiltration failure in peritoneal dialysis (PD). We investigated the role of CTGF in PD-associated lymphangiogenesis. A positive correlation was observed between VEGF-C, a major lymphangiogenic growth factor, and CTGF concentration in human PD effluents. CTGF expression positively correlated with expression of lymphatic markers and VEGF-C in human peritoneal biopsies. There was a positive correlation between CTGF and VEGF-C increment in cultured human peritoneal mesothelial cells treated with TGF-β1. The diaphragm is known as a central player in peritoneal lymphatic absorption. CTGF expression also correlated with expression of VEGF-C and lymphatics in a rat diaphragmatic fibrosis model induced by chlorhexidine gluconate (CG). Furthermore, CTGF gene deletion reduced VEGF-C expression and peritoneal lymphangiogenesis in the mouse CG model. Our results suggest a close relationship between CTGF and PD-associated lymphangiogenesis.

Free Research Field

腎臓病

Academic Significance and Societal Importance of the Research Achievements

腹膜透析に伴う腹膜線維症は、患者の生命予後を悪化させる除水機能不全を合併し、そのメカニズムと治療法の開発が望まれている。これまで除水機能不全の対策は、血管新生と血管透過性亢進に着目されてきたが、我々のリンパ管新生を治療標的とした試みは独創的な研究である。CTGFの抑制治療はさまざまな腎疾患モデルにおいて腎臓線維化を減少させることが報告されてきたが、近年では腹膜線維症モデルでの有効性が注目されつつある。我々のCTGF欠損マウスを用いた腹膜線維症とリンパ管新生におけるCTGF抑制効果の検討は世界に先駆けた研究である。