Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice.
Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice.
Am J Physiol Renal Physiol. 2013 Oct 23;
Authors: Tachibana H, Ogawa D, Sogawa N, Asanuma M, Miyazaki I, Terami N, Hatanaka T, Horiguchi CS, Nakatsuka A, Eguchi J, Wada J, Yamada H, Takei K, Makino H
Abstract
Oxidative stress and inflammation play important roles in diabetic complications, including diabetic nephropathy. 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. Urinary albumin excretion, histological changes, markers for reactive oxygen species (ROS) and kidney inflammation were measured. Murine proximal tubular epithelial (mProx24) cells were used to further 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, despite equivalent levels of hyperglycemia. MT deficiency accelerated interstitial fibrosis and macrophage infiltration into the interstitium in diabetic kidney. Electron microscopy revealed abnormal mitochondrial morphology in proximal tubular epithelial c...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tachibana H, Ogawa D, Sogawa N, Asanuma M, Miyazaki I, Terami N, Hatanaka T, Horiguchi CS, Nakatsuka A, Eguchi J, Wada J, Yamada H, Takei K, Makino H Tags: Am J Physiol Renal Physiol Source Type: research