Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

TNF-α plus IL-1β Induces Opposite Regulation of Hemichannels and Gap Junctions in Mesangial Cells Through a RhoA/ROCK-dependent Pathway

Version 1 : Received: 29 October 2021 / Approved: 29 October 2021 / Online: 29 October 2021 (13:12:44 CEST)

How to cite: Lucero, C.M.; León, M.A.; Fernández, P.; Orellana, J.A.; Velarde, V.; Sáez, J.C.; Gómez, G.I. TNF-α plus IL-1β Induces Opposite Regulation of Hemichannels and Gap Junctions in Mesangial Cells Through a RhoA/ROCK-dependent Pathway. Preprints 2021, 2021100455 (doi: 10.20944/preprints202110.0455.v1). Lucero, C.M.; León, M.A.; Fernández, P.; Orellana, J.A.; Velarde, V.; Sáez, J.C.; Gómez, G.I. TNF-α plus IL-1β Induces Opposite Regulation of Hemichannels and Gap Junctions in Mesangial Cells Through a RhoA/ROCK-dependent Pathway. Preprints 2021, 2021100455 (doi: 10.20944/preprints202110.0455.v1).

Abstract

Connexin 43 (Cx43) is expressed in kidneys and constitutes a feedforward mechanism leading to inflammation in other tissues where they form hemichannels and gap junction channels. However, the possible functional relationship between these membrane channels and their role in damaged renal cells remains unknown. Here, analyses of ethidium uptake and thiobarbituric acid reactive species revealed that TNF-α plus IL-1β increase Cx43 hemichannel activity and oxidative stress in MES-13 cells, a cell line derived from mesangial cells. The latter also was accompanied by a reduction in gap junctional communication, whereas western blotting analysis showed a progressive increase of phosphorylated MYPT (a substrate of RhoA/ROCK) and Cx43 upon TNF-α/IL-1β treatment. Additionally, inhibition of RhoA/ROCK strongly diminished the TNF-α/IL-1β-induced activation of Cx43 hemichannels and reduction in gap junctional coupling. We propose that activation of Cx43 hemichannels and inhibition of cell coupling during pro-inflammatory conditions could contribute to oxidative stress and damage of mesangial cells via the RhoA/ROCK pathway.

Keywords

connexin hemichannel; gap junction; oxidative stress; Inflammatory receptors; Fasudil; Y-27632.

Subject

LIFE SCIENCES, Biophysics

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