Regulator of Calcineurin 1 Isoform 4 (RCAN1.4) Is Overexpressed in the Glomeruli of Diabetic Mice.
10.4196/kjpp.2011.15.5.299
- Author:
Chorong JANG
1
;
Ji Hee LIM
;
Cheol Whee PARK
;
Young Jin CHO
Author Information
1. Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea. haechee@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
RCAN1;
Calcineurin;
Mesangial cell;
Diabetic nephropathy;
Extracellular matrix
- MeSH:
Aluminum Hydroxide;
Animals;
Calcineurin;
Carbonates;
Cyclosporine;
Diabetic Nephropathies;
Extracellular Matrix;
Glycosylation End Products, Advanced;
Hypertrophy;
Interleukin-1beta;
Kidney;
Mesangial Cells;
Mice;
RNA, Messenger;
Serum Albumin;
Serum Albumin, Bovine;
Transfection;
Tumor Necrosis Factor-alpha
- From:The Korean Journal of Physiology and Pharmacology
2011;15(5):299-305
- CountryRepublic of Korea
- Language:English
-
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-1beta (IL-1beta), 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-1beta 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.
