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Connexin43 mediates NF-κB signalling activation induced by high glucose in GMCs: involvement of c-Src
BACKGROUND: Nuclear 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 gl...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699363/ https://www.ncbi.nlm.nih.gov/pubmed/23718910 http://dx.doi.org/10.1186/1478-811X-11-38 |
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author | Xie, Xi Lan, Tian Chang, Xiuting Huang, Kaipeng Huang, Juan Wang, Shaogui Chen, Cheng Shen, Xiaoyan Liu, Peiqing Huang, Heqing |
author_facet | Xie, Xi Lan, Tian Chang, Xiuting Huang, Kaipeng Huang, Juan Wang, Shaogui Chen, Cheng Shen, Xiaoyan Liu, Peiqing Huang, Heqing |
author_sort | Xie, Xi |
collection | PubMed |
description | BACKGROUND: Nuclear 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. RESULTS: We 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. CONCLUSIONS: In 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. |
format | Online Article Text |
id | pubmed-3699363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-36993632013-07-03 Connexin43 mediates NF-κB signalling activation induced by high glucose in GMCs: involvement of c-Src Xie, Xi Lan, Tian Chang, Xiuting Huang, Kaipeng Huang, Juan Wang, Shaogui Chen, Cheng Shen, Xiaoyan Liu, Peiqing Huang, Heqing Cell Commun Signal Research BACKGROUND: Nuclear 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. RESULTS: We 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. CONCLUSIONS: In 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. BioMed Central 2013-05-29 /pmc/articles/PMC3699363/ /pubmed/23718910 http://dx.doi.org/10.1186/1478-811X-11-38 Text en Copyright © 2013 Xie et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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. |
spellingShingle | Research Xie, Xi Lan, Tian Chang, Xiuting Huang, Kaipeng Huang, Juan Wang, Shaogui Chen, Cheng Shen, Xiaoyan Liu, Peiqing Huang, Heqing Connexin43 mediates NF-κB signalling activation induced by high glucose in GMCs: involvement of c-Src |
title | Connexin43 mediates NF-κB signalling activation induced by high glucose in GMCs: involvement of c-Src |
title_full | Connexin43 mediates NF-κB signalling activation induced by high glucose in GMCs: involvement of c-Src |
title_fullStr | Connexin43 mediates NF-κB signalling activation induced by high glucose in GMCs: involvement of c-Src |
title_full_unstemmed | Connexin43 mediates NF-κB signalling activation induced by high glucose in GMCs: involvement of c-Src |
title_short | Connexin43 mediates NF-κB signalling activation induced by high glucose in GMCs: involvement of c-Src |
title_sort | connexin43 mediates nf-κb signalling activation induced by high glucose in gmcs: involvement of c-src |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699363/ https://www.ncbi.nlm.nih.gov/pubmed/23718910 http://dx.doi.org/10.1186/1478-811X-11-38 |
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