Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, China.
School of Basic Medicine, Central South University, Changsha 410078, China.
Acta Biochim Biophys Sin (Shanghai). 2024 May 25;56(5):753-762. doi: 10.3724/abbs.2024026.
Adhesion molecules play critical roles in maintaining the structural integrity of the airway epithelium in airways under stress. Previously, we reported that catenin alpha-like 1 (CTNNAL1) is downregulated in an asthma animal model and upregulated at the edge of human bronchial epithelial cells (HBECs) after ozone stress. In this work, we explore the potential role of CTNNAL1 in the structural adhesion of HBECs and its possible mechanism. We construct a CTNNAL1 mouse model with CTNNAL1-RNAi recombinant adeno-associated virus (AAV) in the lung and a -silencing cell line stably transfected with CTNNAL1-siRNA recombinant plasmids. Hematoxylin and eosin (HE) staining reveals that CTNNAL1 mice have denuded epithelial cells and structural damage to the airway. Silencing of in HBECs inhibits cell proliferation and weakens extracellular matrix adhesion and intercellular adhesion, possibly through the action of the cytoskeleton. We also find that the expressions of the structural adhesion-related molecules E-cadherin, integrin β1, and integrin β4 are significantly decreased in ozone-treated cells than in vector control cells. In addition, our results show that the expression levels of RhoA/ROCK1 are decreased after silencing. Treatment with Y27632, a ROCK inhibitor, abolished the expressions of adhesion molecules induced by ozone in CTNNAL1-overexpressing HBECs. Overall, the findings of the present study suggest that CTNNAL1 plays a critical role in maintaining the structural integrity of the airway epithelium under ozone challenge, and is associated with epithelial cytoskeleton dynamics and the expressions of adhesion-related molecules via the RhoA/ROCK1 pathway.
黏附分子在应激状态下的气道中维持气道上皮结构完整性方面发挥着关键作用。先前我们报道过，钙黏蛋白α样 1（CTNNAL1）在哮喘动物模型中下调，而在臭氧应激后人支气管上皮细胞（HBEC）的边缘上调。在这项工作中，我们探讨了 CTNNAL1 在 HBEC 结构黏附中的潜在作用及其可能的机制。我们构建了一个 CTNNAL1 敲低的小鼠模型，使用携带 CTNNAL1-RNAi 的重组腺相关病毒（AAV）在肺部，以及一个稳定转染 CTNNAL1-siRNA 重组质粒的 -沉默细胞系。苏木精和伊红（HE）染色显示 CTNNAL1 敲低的小鼠有上皮细胞剥脱和气道结构损伤。在 HBEC 中沉默 会抑制细胞增殖，并削弱细胞外基质黏附和细胞间黏附，这可能是通过细胞骨架的作用。我们还发现，臭氧处理的细胞中结构黏附相关分子 E-钙黏蛋白、整合素β1 和整合素β4 的表达明显低于载体对照细胞。此外，我们的结果表明，沉默 后 RhoA/ROCK1 的表达水平降低。用 ROCK 抑制剂 Y27632 处理可消除 CTNNAL1 过表达 HBEC 中臭氧诱导的黏附分子的表达。总之，本研究结果表明，CTNNAL1 在臭氧挑战下维持气道上皮结构完整性方面发挥着关键作用，并且与上皮细胞骨架动力学以及通过 RhoA/ROCK1 通路表达黏附相关分子有关。
