Protein kinase CK2α catalytic subunit ameliorates diabetic renal inflammatory fibrosis via NF-κB signaling pathway

Activation of casein kinase 2 (CK2) is closely linked to the body disturbance of carbohydrate metabolism and inflammatory reaction. The renal chronic inflammatory reaction in the setting of diabetes is one of the important hallmarks of diabetic renal fibrosis. However, it remains unknown whether CK2 influences the process of diabetic renal fibrosis. The current study is aimed to investigate if CK2 alpha ameliorates renal inflammatory fibrosis in diabetes via NF-kappa B pathway. To explore potential regulatory mechanism of CK2 alpha, the expression and activity of CK2 alpha, which were studied by plasmid transfection, selective inhibitor, small-interfering RNA (siRNA) and adenovirus infection in vitro or in vivo, were analyzed by means of western blotting (WB), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA). The following findings were observed: (1) Expression of CK2 alpha, was upregulated in kidneys of di:0:lb and KKAy diabetic mice; (2) Inhibition of CK2 alpha kinase activity or knockdown of CK2 alpha protein expression suppressed high glucose-induced expressions of FN and ICAM-1 in glomerular mesangial cells (GMCs); (3) Inhibition of CK2 alpha kinase activity or knockdown of CK2 alpha protein expression not only restrained hcB degradation, but also suppressed HG-induced nuclear accumulation, transcriptional activity and DNA binding activity of NF-kappa B in GMCs; (4) Treatment of TBB or CK2 alpha RNAi adenovirus infection ameliorated renal fibrosis in diabetic animals; (5) Treatment of TBB or CK2 alpha RNAi adenovirus infection suppressed hcB degradation and NF-kappa B nuclear accumulation in glomeruli of diabetic animals. This study indicates the essential role of CK2 alpha in regulating the diabetic renal pathological process of inflammatory fibrosis via NF-kappa B pathway, and inhibition of CK2 alpha may serve as a promising therapeutic strategy for diabetic nephropathy. (C) 2017 Elsevier Inc. All rights reserved.