Therapeutic effects of uromodulin in renal diseases

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09276
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Showa University
• Principal Investigator: Iyoda Masayuki 昭和大学, 医学部, 准教授 (20384365)
• Co-Investigator(Kenkyū-buntansha): 鈴木 泰平 昭和大学, 医学部, 助教 (10749948) ; 柴田 孝則 昭和大学, 医学部, 教授 (70221299)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ウロモジュリン / 抗GBM抗体腎炎 / 近位尿細管上皮細胞 / 抗炎症効果 / p38 MAPK / MCP-1 / ANCA関連腎炎

Outline of Final Research Achievements

We showed that uromodulin (UMOD) had preventive and therapeutic effects in experimental anti-GBM glomerulonephritis via anti-inflammatory effects. These results suggest that UMOD may be a novel therapeutic strategy for anti-GBM glomerulonephritis. In addition, we found that UMOD binds to SRB-1 in proximal tubular epithelial cells and inhibites TNF-α-induced MCP-1 protein and mRNA expressions via p38 signaling pathway inhibition. These results indicate that UMOD acts protectively against renal tubular injury. Furtheremore, we clarified the clinical significance of UMOD in ANCA-associated glomerulonephritis (AAG). A negative correlation between serum UMOD levels and the urinary protein levels as well as serum Cr levels, and positive correlation between serum UMOD levels and eGFR were found. Lower serum UMOD levels predicted severe pathological classes independently of serum Cr levels.

Free Research Field

腎炎・ネフローゼ