Nuclear factor-kappa B influences early phase of compensatory lung growth after pneumonectomy in mice

Background: Compensatory lung growth (CLG) is a well-established lung regeneration model. However, the sequential mechanisms, including unknown molecular triggers or regulators, remain unclear. Nuclear factor-kappa B (NF-kappa B) is known to be essential for inflammation and tissue regeneration; therefore, we investigated the role of NF-kappa B in CLG. Methods: C57BL/6 J mice underwent either a left pneumonectomy or a thoracotomy (n = 77). Gene microarray analysis was performed to detect genes that were upregulated at 12 h after pneumonectomy. NF-kappa B protein expression was examined by immunohistochemistry and Western blot. To investigate the influence of NF-kappa B on CLG, either an NF-kappa B inhibitor SN50 or saline was administered following pneumonectomy and the degree of CLG was evaluated in each group by measuring the lung dry weight index (LDWI) and the mean linear intercept. Results: Gene microarray analysis identified 11 genes that were significantly but transiently increased at 12 h after pneumonectomy. Among the 11 genes, NF-kappa B was selected based on its reported functions. Western blot analysis showed that NF-kappa B protein expression after pneumonectomy was significantly higher at 12 h compared to 48 h. Additionally, NF-kappa B protein expression at 12 h after pneumonectomy was significantly higher than at both 12 and 48 h after thoracotomy (p < 0.029 for all). NF-kappa B protein expression, evaluated through immunohistochemistry, was expressed mainly in type 2 alveolar epithelial cells and was significant increased 12 h after pneumonectomy compared to 48 h after pneumonectomy and both 12 and 48 h after thoracotomy (p < 0.001 for all). SN50 administration following pneumonectomy induced a significant decrease in NF-kappa B expression (p = 0.004) and LDWI compared to the vehicle administration (p = 0.009). Conclusions: This is the first report demonstrating that NF-kappa B signaling may play a key role in CLG. Given its pathway is crucial in tissue regeneration of various organs, NF-kappa B may shed light on identification of molecular triggers or clinically usable key regulators of CLG.