Cortactin Modulates Lung Endothelial Apoptosis Induced by Cigarette Smoke

Area of Science:

• Cell Biology
• Pulmonary Medicine
• Toxicology

Background:

• Cigarette smoke (CS) is a primary cause of Chronic Obstructive Pulmonary Disease (COPD).
• CS induces apoptosis in lung endothelial cells (EC), a key event in COPD pathogenesis.
• Cortactin (CTTN), an actin-binding protein, has reduced mRNA levels in smokers' lungs.

Purpose of the Study:

• To investigate the role of Cortactin (CTTN) in CS-induced mitochondrial reactive oxygen species (ROS) generation and apoptosis in lung EC.
• To explore CTTN's function in lung EC exposed to cigarette smoke condensate (CSC) and e-cigarette condensate.

Main Methods:

• Cultured human lung EC were exposed to CSC and e-cigarette condensate.
• CTTN expression was reduced using siRNA, and its SH3 domain was blocked with a peptide.
• Mitochondrial ROS generation and EC apoptosis were measured.

Main Results:

• CSC exposure induced actin cytoskeleton rearrangement and increased CTTN tyrosine phosphorylation in lung EC.
• CS exposure significantly increased EC mitochondrial ROS and apoptosis.
• Reducing CTTN expression or blocking its SH3 domain exacerbated CSC-induced mitochondrial ROS and apoptosis.
• Similar exacerbation of lung EC apoptosis was observed with e-cigarette condensate exposure.

Conclusions:

• CTTN plays a novel, protective role in modulating lung EC apoptosis induced by CS and e-cigarettes.
• These findings provide new insights into the pathogenesis of COPD.
• CTTN may represent a potential therapeutic target for CS-related lung diseases.