Investigation of molecular mechanisms of endothelial dysfunction underlying CKD and aging kidney

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04838
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kawasaki Medical School
• Principal Investigator: Kashihara Naoki 川崎医科大学, 医学部, 教授 (10233701)
• Co-Investigator(Kenkyū-buntansha): 春名 克祐 川崎医科大学, 医学部, 講師 (40341094) ; 佐藤 稔 川崎医科大学, 医学部, 准教授 (70449891) ; 長洲 一 川崎医科大学, 医学部, 講師 (40412176) ; 城所 研吾 川崎医科大学, 医学部, 講師 (50435020) ; 桑原 篤憲 川崎医科大学, 医学部, 講師 (50368627)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 血管内皮障害 / 慢性炎症 / 線維化 / インフラマソーム / Nrf2 / 酸化ストレス / 慢性腎臓病 / Wnt

Outline of Final Research Achievements

The endothelium and epithelial cells are in close proximity, and there is functional interaction (endothelium / epithelium connection) mutually. We have elucidated the followings; 1) Endothelial dysfunction disrupts endothelium / epithelium relationship, causing two major pathologies of progression of chronic kidney disease, "inflammation" and "fibrosis". 2) NLRP 3-inlammasome pathway and Wnt / β-catenin pathway are involved in this process. 3) NO / cGMP / PKG pathway suppresses NLRP3-inflammasome activation(deeply involved in chronic inflammation) and Wnt / β-catenin pathway activation (fibrosis). 4) Endothelial / epithelial interaction plays an important role in pathogenesis of glomerular lesions and tubulointerstitial injuries in CKD. It is expected that these findings will be utilized in the development of novel strategy to cope with CKD.

Free Research Field

腎臓内科学