The role of Angiopoietin-like protein 2 in renal fibrosis

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860639
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Kumamoto University
• Principal Investigator: Morinaga Jun 熊本大学, その他の研究科, その他 (50459210)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 腎線維化 / ANGPTL2 / TGF-β / 尿細管細胞 / マクロファージ

Outline of Final Research Achievements

Here, we demonstrate a molecular link between chronic inflammation and tissue fibrosis in chronic kidney disease (CKD) progression. Specifically, we report histological analysis indicating abundant expression of angiopoietin-like protein 2 (ANGPTL2) in renal tubule epithelial cells during progression of renal fibrosis. Analysis of collecting duct cells revealed that TGF-β1 increases ANGPTL2 expression by attenuating its repression by the microRNA-221. Conversely, ANGPTL2 increased TGF-β1 expression through α5β1 integrin-mediated activation of extracellular signal-regulated kinase. Furthermore, ANGPTL2 deficiency in a mouse unilateral ureteral obstruction model significantly reduced renal fibrosis by decreasing TGF-β1 signal amplification in kidney.
Our study provides insight into molecular mechanisms underlying chronic inflammation and tissue fibrosis and identifies targets potentially useful for CKD treatment.

Free Research Field

腎臓内科学