Connexin43 mediates NF-κB signalling activation induced by high glucose in GMCs: involvement of c-Src

Cell Communication and Signaling

Research

Kaipeng Huang¹  Xiaoyan Shen¹  Xiuting Chang¹  Heqing Huang¹  Juan Huang¹  Cheng Chen¹  Peiqing Liu¹  Shaogui Wang¹  Xi Xie²  Tian Lan³ 

[1] Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, 510006, Guangzhou, China;Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, 510006, Guangzhou, China;Department of Pharmaceutical Engineering, Ocean College, Hainan University, 570228, Haikou, China;Vascular Biology Institute, Guangdong Pharmaceutical University, 510006, Guangzhou, China;

关键词: Connexin43;    NF-κB signalling;    c-Src;    Diabetic nephropathy;    Inflammation;    Fibronectin;   

DOI  :  10.1186/1478-811X-11-38

 received in 2013-01-08, accepted in 2013-05-10,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundNuclear factor kappa-B (NF-κB) signalling plays an important role in diabetic nephropathy. Altered expression of connexin43 (Cx43) has been found in kidneys of diabetic animals. The aim of the current study was to investigate the role of Cx43 in the activation of NF-κB induced by high glucose in glomerular mesangial cells (GMCs) and to determine whether c-Src is involved in this process.ResultsWe found that downregulation of Cx43 expression induced by high glucose activated NF-κB in GMCs. Orverexpression of Cx43 attenuated NF-κB p65 nuclear translocation induced by high glucose. High glucose inhibited the interaction between Cx43 and c-Src, and enhanced the interaction between c-Src and IκB-α. PP2, a c-Src inhibitor, also inhibited the tyrosine phosphorylation of IκB-α and NF-κB p65 nuclear translocation induced by high glucose. Furthermore, overexpression of Cx43 or inhibition of c-Src attenuated the upregulation of intercellular adhesion molecule-1 (ICAM-1), transforming growth factor-beta 1 (TGF-β1) and fibronectin (FN) expression induced by high glucose.ConclusionsIn conclusion, downregulation of Cx43 in GMCs induced by high glucose activates c-Src, which in turn promotes interaction between c-Src and IκB-α and contributes to NF-κB activation in GMCs, leading to renal inflammation.

【 授权许可】

Unknown   
© Xie et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.