Establishment of new strategy targeting lymphangiogenesis in the patients with renal diseases

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09287
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Aichi Medical University (2017-2018); Nagoya University (2015-2016)
• Principal Investigator: Yasuhiko Ito 愛知医科大学, 医学部, 教授 (60402632)
• Co-Investigator(Kenkyū-buntansha): 水野 正司 名古屋大学, 医学系研究科, 寄附講座教授 (20303638) ; 鈴木 康弘 名古屋大学, 医学系研究科, 寄附講座講師 (20584676) ; 坂田 史子 名古屋大学, 医学系研究科, 特任助教 (20726484) ; 武井 佳史 愛知学院大学, 薬学部, 教授 (70362233)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 腹膜透析 / 腹膜機能不全 / リンパ管新生 / 血管新生 / 炎症

Outline of Final Research Achievements

Appropriate fluid balance is important for good outcomes in patients on peritoneal dialysis. The characteristic features of peritoneal injury with PD are fibrosis, inflammation and neoangiogenesis; however, these precise mechanisms remain unclear.
We investigated the 1) roles and pathophysiology of lymphangiogenesis in PD, 2) relationship between peritoneal fibrosis and angiogenesis, and 3) roles of high salt intake in PD. We conducted the studies using animal models, in vitro studies with mesothelial cells, fibroblasts, and macrophages, and human materials including peritoneal biopsy samples and PD effluent. In animal models Adeno-soluble VEGFR-3 effectively improve the drained volume by suppression of lymphangiogenesis, suggesting thatVEGFR-3 could be the new target to improve UF. Neoangiogenesis is associated with fibrosis by TGF-β1-VEGF-A pathway in mesothelial cells and fibroblasts. High salt intake induces the inflammation leading to the increase of peritoneal transport rates.

Free Research Field

腹膜透析

Academic Significance and Societal Importance of the Research Achievements

腹膜透析(PD)における除水不全の機序、対策が明らかになることによって、PD治療が長期に可能となり、PD患者負担が軽減する。ひいては医療経済にも好影響を与える。