Possible roles of tumor necrosis factor-alpha and angiotensin II type 1 receptor on high glucose-induced damage in renal proximal tubular cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 23591219
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kawasaki Medical School (2013-2014); Kochi University (2011-2012)
• Principal Investigator: TAKAO TOSHIHIRO 川崎医科大学, 医学部, 教授 (00243824)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: 近位尿細管 / グルコース / アンジオテンシン受容体 / 酸化ストレス / 腫瘍壊死因子

Outline of Final Research Achievements

High glucose treatment (30 mM) significantly increased N-acetyl-beta-glucosaminidase (NAG) release, tumor necrosis factor (TNF)alpha/angiotensin II concentrations in cell media and p22phox protein levels compared with those in regular glucose medium (5.6 mM). Candesartan, an angiotensin II type 1 receptor (AT1R) blocker, showed a significant reduction on high glucose-induced NAG release, TNFalpha concentrations and p22phox protein levels in human renal proximal tubular epithelial cells (HK2 cells). In addition, significant decreases of NAG release, TNFalpha concentrations and p22phox protein levels in HK2 cells were observed in high glucose-treated group with thalidomide. AT1R knockdown with siRNA markedly reversed high glucose, angiotensin II or TNFalpha-induced p22phox protein levels in HK2 cells. TNFalpha may be involved in high glucose-induced renal tubular damage in HK2 cells possibly via AT1 receptor signaling.

Free Research Field

内分泌代謝学