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Particulate matter (PM) air pollution is a known factor to exacerbate cardiopulmonary diseases. We previously demonstrated that PM mediated endothelial injury and barrier disruption via modulation of the endothelial cytoskeleton

Particulate matter (PM) air pollution is a known factor to exacerbate cardiopulmonary diseases. We previously demonstrated that PM mediated endothelial injury and barrier disruption via modulation of the endothelial cytoskeleton and cell-cell junctions, while the effects of PM exposure on cell-cell communication and gap junction activity are still unknown. This study is focused on the characterization of PM-mediated endothelial dysfunction via Connexin 43 (Cx43), the most abundant Gap junction protein expressed in lung endothelial cells (ECs). PM exposure induces a time-dependent elevation of Cx43 in human lung ECs, at both mRNA and protein levels. N-acetyl-cysteine (NAC), an ROS scavenger, significantly suppresses PM-induced Cx43 expression. Membrane-associated and ER/ Golgi apparatus Cx43 protein are elevated upon PM challenge. In addition, PM also activates the gap junction activity, indicated by the transportation of green fluorescence dye between two adjacent ECs. Moreover, GAP27, a selective Cx43 channel inhibitor, attenuates PM-reduced human lung EC barrier disruption, measured by trans-endothelial electrical resistance (TER) with an electric cell-substrate impedance sensing system. Moreover, knock-down the expression of Cx43 by its selective siRNA alleviates PM-induced MLC phosphorylation. These results highly suggest that Cx43 plays a key role in PM-mediated endothelial barrier disruption and signal transduction. Cx43 may deputy as a therapeutic target in PM-mediated cardiopulmonary disorders.

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