Particulate matter increases connexin 43 expression and exacerbates endothelial barrier disruption.

Area of Science:

• Environmental Health
• Cell Biology
• Cardiopulmonary Research

Background:

• Particulate matter (PM) air pollution exacerbates cardiopulmonary diseases.
• PM exposure disrupts endothelial cell cytoskeleton and junctions.
• The impact of PM on endothelial cell-cell communication and gap junctions remains unclear.

Purpose of the Study:

• To investigate the role of connexin 43 (Cx43) in PM-induced endothelial dysfunction.
• To characterize PM effects on gap junction activity in lung endothelial cells (ECs).

Main Methods:

• Cultured human lung ECs were exposed to a well-characterized PM sample.
• Analyzed Cx43 expression at mRNA and protein levels.
• Assessed gap junction activity via dye transfer and EC barrier function using trans-endothelial electrical resistance (TER).

Main Results:

• PM exposure increased Cx43 expression in a time-dependent manner, modulated by ROS scavenger N-acetylcysteine (NAC).
• PM elevated Cx43 on the plasma membrane and ER/Golgi, increased gap junction activity, and disrupted EC barrier function.
• Cx43 inhibition (GAP27) and knockdown attenuated PM-induced barrier disruption and myosin light chain (MLC) phosphorylation.

Conclusions:

• Cx43 is crucial in PM-mediated endothelial barrier disruption and signal transduction.
• Cx43 represents a potential therapeutic target for PM-related cardiopulmonary disorders.