TNF-alpha Plus IL-1 beta Induces Opposite Regulation of Cx43 Hemichannels and Gap Junctions in Mesangial Cells through a RhoA/ROCK-Dependent Pathway
Abstract
Connexin 43 (Cx43) is expressed in kidney tissue where it forms hemichannels and gap junction channels. However, the possible functional relationship between these membrane channels and their role in damaged renal cells remains unknown. Here, analysis of ethidium uptake and thiobarbituric acid reactive species revealed that treatment with TNF-alpha plus IL-1 beta increases Cx43 hemichannel activity and oxidative stress in MES-13 cells (a cell line derived from mesangial cells), and in primary mesangial cells. The latter was also accompanied by a reduction in gap junctional communication, whereas Western blotting assays showed a progressive increase in phosphorylated MYPT (a target of RhoA/ROCK) and Cx43 upon TNF-alpha/IL-1 beta treatment. Additionally, inhibition of RhoA/ROCK strongly antagonized the TNF-alpha/IL-1 beta-induced activation of Cx43 hemichannels and reduction in gap junctional coupling. We propose that activation of Cx43 hemichannels and inhibition of cell-cell coupling during pro-inflammatory conditions could contribute to oxidative stress and damage of mesangial cells via the RhoA/ROCK pathway.
Más información
Título según WOS: | ID WOS:000851150600001 Not found in local WOS DB |
Título de la Revista: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES |
Volumen: | 23 |
Número: | 17 |
Editorial: | MDPI Open Access Publishing |
Fecha de publicación: | 2022 |
DOI: |
10.3390/ijms231710097 |
Notas: | ISI |