Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 17, Pages -Publisher
MDPI
DOI: 10.3390/ijms231710097
Keywords
connexin hemichannel; gap junction; oxidative stress; inflammatory receptors; Fasudil; Y-27632
Funding
- CONICYT Ph.D. fellowship [21120081]
- FONDECYT [1210375, 1191329]
- Iniciativa Cientifica Milenio (ICM)-ECONOMIA from Chile [P09-022-F]
- FONDECYT INICIACION [11200584]
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This study found that the activation of Cx43 hemichannels and inhibition of cell-cell coupling during inflammation may contribute to oxidative stress and damage of mesangial cells through the RhoA/ROCK pathway.
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.
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