Wound repair and proliferation of bronchial epithelial cells regulated by CTNNAL1
Wound repair and proliferation of bronchial epithelial cells regulated by CTNNAL1
复制标题
CTNNAL1调控支气管上皮细胞的损伤修复和增殖
DOI：
10.1002/jcb.21461
复制
发表时间：
2008-02-15
影响因子：
4
通讯作者：
Liu, Hui-Jun
中科院分区：
文献类型：
--
作者：
Xiang, Yang;Tan, Yu-Rong;Liu, Hui-Jun
黏附分子在气道高反应性(AHR)或气道炎症中起重要作用。我们先前的研究表明，黏附分子连环蛋白α-样蛋白1(CTNNAL1)与哮喘易感性密切相关，但其生物学功能或意义尚不清楚。本研究采用卵清蛋白致敏的哮喘模型，观察了小鼠肺组织CTNNAL1mRNA表达的时空分布，发现CTNNAL1mRNA表达水平与肺阻力呈显著负相关(R(L))。为探讨CTNNAL1在呼吸道中的作用，应用反义寡核苷酸(ASO)技术观察了CTNNAL1对人支气管上皮细胞(HBEC)增殖和损伤修复活性的影响。结果表明：(1)CTNNAL1 ASO可减慢HBEC的修复速度和增殖速度；(2)CTNNAL1在机械损伤区边缘细胞上的表达增加；(3)细胞外基质成分纤维连接蛋白(FN)可明显促进HBEC的修复活性和增殖，该作用可被CTNNAL1 ASO所阻断；(4)Western印迹显示FN可促进FAK的磷酸化，CTNNAL1 ASO也可抑制这一作用。综上所述，CTNNAL1mRNA的表达水平与气道阻力高度相关，CTNNAL1可能参与了HBEC的损伤修复和增殖。此外，它可能参与FN介导的细胞-细胞外黏附及其信号转导。
Adhesion molecules play vital roles in airway hyperresponsiveness (AHR) or airway inflammation. Our previous study indicated that adhesion molecule catenin alpha-like 1 (CTNNAL1) is relevant closely to asthma susceptibility, but its biological function or significance is still unclear. In the present study, we observed the temporal and spatial distribution of CTNNAL1 expression in mouse lung tissue with the OVA-sensitized asthma model and found that the level of CTNNAL1 mRNA showed a prominent negative correlation with pulmonary resistance (R(L)). To study the function of CTNNAL1 in airway, effects of CTNNAL1 on proliferation and wound repair activity of human bronchial epithelial cells (HBEC) was investigated with antisense oligonucleotide (ASO) technique. The results showed that: (1) CTNNAL1 ASO could decelerate the repairing velocity and proliferation of HBEC; (2) CTNNAL1 expression was increased on the edge cells of mechanic wounded area in culture; (3) extracellular matrix component fibronectin (Fn) obviously promoted wound repair activity and proliferation of HBEC, which could be blocked by CTNNAL1 ASO; (4) Western blot showed that Fn could promote FAK phosphorylation, which also be inhibited by CTNNAL1 ASO. In conclusion, the level of CTNNAL1 mRNAexpression is highly correlated to airway resistance; CTNNAL1 may contribute to the wound repair and proliferation of HBEC. Furthermore, it may serve to Fn mediated cell-extracellular adhesion and its signal transduction.