| First Author | Huang J | Year | 2017 |
| Journal | Biochem Pharmacol | Volume | 132 |
| Pages | 102-117 | PubMed ID | 28237649 |
| Mgi Jnum | J:255860 | Mgi Id | MGI:6107290 |
| Doi | 10.1016/j.bcp.2017.02.016 | Citation | Huang J, et al. (2017) Protein kinase CK2alpha catalytic subunit ameliorates diabetic renal inflammatory fibrosis via NF-kappaB signaling pathway. Biochem Pharmacol 132:102-117 |
| abstractText | 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 CK2alpha ameliorates renal inflammatory fibrosis in diabetes via NF-kappaB pathway. To explore potential regulatory mechanism of CK2alpha, the expression and activity of CK2alpha, 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 CK2alpha was upregulated in kidneys of db/db and KKAy diabetic mice; (2) Inhibition of CK2alpha kinase activity or knockdown of CK2alpha protein expression suppressed high glucose-induced expressions of FN and ICAM-1 in glomerular mesangial cells (GMCs); (3) Inhibition of CK2alpha kinase activity or knockdown of CK2alpha protein expression not only restrained IkappaB degradation, but also suppressed HG-induced nuclear accumulation, transcriptional activity and DNA binding activity of NF-kappaB in GMCs; (4) Treatment of TBB or CK2alpha RNAi adenovirus infection ameliorated renal fibrosis in diabetic animals; (5) Treatment of TBB or CK2alpha RNAi adenovirus infection suppressed IkappaB degradation and NF-kappaB nuclear accumulation in glomeruli of diabetic animals. This study indicates the essential role of CK2alpha in regulating the diabetic renal pathological process of inflammatory fibrosis via NF-kappaB pathway, and inhibition of CK2alpha may serve as a promising therapeutic strategy for diabetic nephropathy. |
