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http://dx.doi.org/10.4196/kjpp.2011.15.5.299

Regulator of Calcineurin 1 Isoform 4 (RCAN1.4) Is Overexpressed in the Glomeruli of Diabetic Mice  

Jang, Cho-Rong (Department of Pharmacology, College of Medicine, The Catholic University of Korea)
Lim, Ji-Hee (Depratment of Internal Medicine, College of Medicine, The Catholic University of Korea)
Park, Cheol-Whee (Depratment of Internal Medicine, College of Medicine, The Catholic University of Korea)
Cho, Young-Jin (Department of Pharmacology, College of Medicine, The Catholic University of Korea)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.15, no.5, 2011 , pp. 299-305 More about this Journal
Abstract
Calcineurin (CaN) is activated in diabetes and plays a role in glomerular hypertrophy and extracellular matrix (ECM) accumulation. Here, kidneys from diabetic model mice were investigated for the expression of the regulator of CaN 1 (RCAN1) isoform 4 (RCAN1.4) which had been shown to be transcriptionally upregulated by CaN activation. We found the increased immunoreactivity for RCAN1 in the glomerular cells of db/db mice and streptozotocin-induced diabetic mice. In concordance, the expression of RCAN1 protein and RCAN1.4 mRNA were elevated in the whole kidney sample from db/db mice. Interleukin-$1{\beta}$ (IL-$1{\beta}$), tumor necrosis factor-${\alpha}$, and glycated albumin (AGE-BSA) were identified as inducers of RCAN1.4 in mesangial cells. Pretreatment of cyclosporine A blocked the increases of RCAN1.4 stimulated by IL-$1{\beta}$ or AGE-BSA, suggesting that activation of CaN is required for the RCAN1.4 induction. Stable transfection of RCAN1.4 in Mes-13 mesangial cells upregulated several factors relevant to ECM production and degradation. These results suggested that RCAN1.4 might act as a link between CaN activation and ECM turnover in diabetic nephropathy.
Keywords
RCAN1; Calcineurin; Mesangial cell; Diabetic nephropathy; Extracellular matrix;
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