The role of metallothionein in diabetic nephropathy

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461223
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Okayama University
• Principal Investigator: Ogawa Daisuke 岡山大学, 医歯(薬)学総合研究科, 准教授 (70535195)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 糖尿病性腎症 / 酸化ストレス / 炎症

Outline of Final Research Achievements

Metallothionein (MT) is induced in proximal tubular epithelial cells as an antioxidant in diabetic kidney; however, the role of MT in renal function remains unclear. We therefore investigated if MT deficiency accelerates diabetic nephropathy through oxidative stress and inflammation. Diabetes was induced by streptozotocin injection in MT-deficient (MT-/-) and MT+/+ mice. Murine proximal tubular epithelial cells were used to elucidate the role of MT under high-glucose conditions. Parameters of diabetic nephropathy and markers of ROS and inflammation were accelerated in diabetic MT-/- mice compared with diabetic MT+/+ mice. In vitro studies demonstrated that knockdown of MT by small interfering RNA enhanced mitochondrial ROS generation and inflammation-related gene expression in cultured cells under high-glucose conditions. These results suggest that MT may play a key role in protecting the kidney against high glucose-induced ROS and subsequent inflammation in diabetic nephropathy.

Free Research Field

医歯薬学