• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2019 Fiscal Year Final Research Report

Development of novel therapeutic approaches for glomerulosclerosis using genetically modified mice

Research Project

  • PDF
Project/Area Number 17K08442
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionMie University

Principal Investigator

Gabazza Corina  三重大学, 医学系研究科, 特任講師(研究担当) (10750656)

Co-Investigator(Kenkyū-buntansha) Gabazza Esteban  三重大学, 医学系研究科, 教授 (00293770)
安間 太郎  三重大学, 医学系研究科, 助教 (80773887)
Project Period (FY) 2017-04-01 – 2020-03-31
Keywords組織線維化 / 転写因子 / Akt経路 / Smad2/3 / トロンボモジュリン / TGFβ1 / G-タンパク質共役受容体 / 腎不全
Outline of Final Research Achievements

In present investigation, we evaluated the effect of recombinant human thrombomodulin on the kidney fibrosis and renal failure using a transgenic mouse over-expressing the complete DNA sequence of human transforming growth factor (TGF)β1 specifically in the renal glomeruli. The TGFβ1 transgenic mice treated with the recombinant human thrombomodulin showed significant decreased glomerular and tubulointerstitial deposition of extracellular matrix protein including collagen and fibronectin, reduced renal expression of pro-fibrotic and inflammatory cytokines and decreased activation of the complement system. In vitro and in vivo experiments showed that recombinant human thrombomodulin blocked apoptosis and the epithelial-mesenchymal transition-of podocytes by binding to GPR15 and by subsequent activation of the Akt signaling pathway and blockade of Smad proteins. These results suggest the potential of recombinant human thrombomodulin as a therapeutic drug for chronic kidney disease.

Free Research Field

腎臓内科

Academic Significance and Societal Importance of the Research Achievements

糖尿病、高血圧等の慢性疾患による腎症の悪化に伴い、血液透析を余儀なくされる患者数は増加の一途を辿り、年間約1万人以上の患者が新規透析導入患者とされている。これらの慢性疾患から腎不全に移行した血液透析患者の予後は、他疾患に比較して著しく悪く、その予後改善の対策が急務と考えられる。本研究においては、慢性腎臓疾患に対する新たな治療戦略の開発に繋がっている。従って、本研究で得た成果は、世界に先駆けての腎線維症に対する新規抗線維化剤の開発において画期的な基礎的情報を提供するものと考えられる。

URL: 

Published: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi