Protein kinase CK2α catalytic subunit ameliorates diabetic renal inflammatory fibrosis via NF-κB signaling pathway
Protein kinase CK2α catalytic subunit ameliorates diabetic renal inflammatory fibrosis via NF-κB signaling pathway
复制标题
蛋白激酶CK2α催化亚基通过NF-κB信号通路改善糖尿病肾炎症纤维化
DOI：
10.1016/j.bcp.2017.02.016
复制
发表时间：
2017-05-15
影响因子：
5.8
通讯作者：
Huang, Heqing
中科院分区：
文献类型：
--
作者：
Huang, Junying;Chen, Zhiquan;Huang, Heqing
酪蛋白激酶2（casein kinase 2，CK 2）的激活与机体糖代谢紊乱和炎症反应密切相关。糖尿病患者肾脏慢性炎症反应是糖尿病肾纤维化的重要标志之一。然而，CK 2是否影响糖尿病肾纤维化的过程仍不清楚。本研究旨在探讨CK 2 α是否通过NF-κ B B通路改善糖尿病肾脏炎性纤维化。为探讨CK 2 α的潜在调控机制，分别采用质粒转染、选择性抑制剂、小干扰RNA（siRNA）和腺病毒感染等方法研究了CK 2 α在体外和体内的表达和活性，并采用免疫印迹（WB）、双荧光素酶报告基因分析和电泳迁移率变动分析（EMSA）等方法进行了研究。结果发现：（1）糖尿病小鼠肾脏CK 2 α表达上调，（2）抑制CK 2 α激酶活性或敲低CK 2 α蛋白表达可抑制高糖诱导的肾小球系膜细胞（GMCs）FN和ICAM-1的表达;（3）抑制CK 2 α激酶活性或敲低CK 2 α蛋白表达不仅抑制hcB降解，而且抑制HG诱导的核积聚，（4）TBB或CK 2 α RNAi腺病毒感染的治疗改善了糖尿病动物的肾纤维化;（5）TBB或CK 2 α RNAi腺病毒感染治疗抑制糖尿病动物肾小球中hc B降解和NF-κ B核积聚。提示CK 2 α通过NF-κ B B通路在糖尿病肾脏炎症纤维化的病理过程中起重要作用，抑制CK 2 α可能成为糖尿病肾病治疗的一种新策略。(C)2017爱思唯尔公司All rights reserved.
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.