Department of General Thoracic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8606, Japan.
J Biomed Sci. 2017 Jul 5;24(1):41. doi: 10.1186/s12929-017-0350-z.
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-κB) is known to be essential for inflammation and tissue regeneration; therefore, we investigated the role of NF-κB in CLG.
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-κB protein expression was examined by immunohistochemistry and Western blot. To investigate the influence of NF-κB on CLG, either an NF-κB 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.
Gene microarray analysis identified 11 genes that were significantly but transiently increased at 12 h after pneumonectomy. Among the 11 genes, NF-κB was selected based on its reported functions. Western blot analysis showed that NF-κB protein expression after pneumonectomy was significantly higher at 12 h compared to 48 h. Additionally, NF-κB 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-κB 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-κB expression (p = 0.004) and LDWI compared to the vehicle administration (p = 0.009).
This is the first report demonstrating that NF-κB signaling may play a key role in CLG. Given its pathway is crucial in tissue regeneration of various organs, NF-κB may shed light on identification of molecular triggers or clinically usable key regulators of CLG.
代偿性肺生长（CLG）是一种成熟的肺再生模型。然而，包括未知的分子触发物或调节剂在内的连续机制仍不清楚。核因子-κB（NF-κB）已知对炎症和组织再生至关重要；因此，我们研究了 NF-κB 在 CLG 中的作用。
C57BL/6J 小鼠行左肺切除术或开胸术（n=77）。进行基因微阵列分析以检测肺切除后 12 小时上调的基因。通过免疫组织化学和 Western blot 检测 NF-κB 蛋白表达。为了研究 NF-κB 对 CLG 的影响，在肺切除术后给予 NF-κB 抑制剂 SN50 或生理盐水，并通过测量肺干重指数（LDWI）和平均线性截距来评估每组 CLG 的程度。
基因微阵列分析鉴定出肺切除后 12 小时显著但短暂增加的 11 个基因。在这 11 个基因中，根据其报道的功能选择了 NF-κB。Western blot 分析显示，肺切除后 12 小时 NF-κB 蛋白表达明显高于 48 小时。此外，肺切除后 12 小时 NF-κB 蛋白表达明显高于开胸术后 12 小时和 48 小时（所有 p<0.029）。通过免疫组织化学评估的 NF-κB 蛋白表达主要在 II 型肺泡上皮细胞中表达，与肺切除后 48 小时相比，肺切除后 12 小时 NF-κB 蛋白表达明显增加（所有 p<0.001）。与载体给药相比，肺切除术后给予 SN50 可显著降低 NF-κB 表达（p=0.004）和 LDWI（p=0.009）。
这是第一项表明 NF-κB 信号可能在 CLG 中发挥关键作用的报告。鉴于其途径对各种器官的组织再生至关重要，NF-κB 可能为鉴定 CLG 的分子触发物或临床可用的关键调节剂提供线索。
