Centre de recherche, Institut universitaire de cardiologie et de pneumologie de Québec, Sainte-Foy, Québec, QC, Canada.
Allergy. 2010 Nov;65(11):1438-45. doi: 10.1111/j.1398-9995.2010.02376.x.
Bronchial epithelium is considered a key player in coordinating airway wall remodelling. The function of epithelial cells can be modulated by the underlying fibroblasts through autocrine and paracrine mechanisms.
To investigate the effect of phenotypic changes in bronchial fibroblasts from asthmatic subjects on epithelial cell proliferation.
Epithelial cells and fibroblasts derived from bronchial biopsies of asthmatic and healthy controls were cultured in an engineered model. Proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium-bromid (MTT). Epidermal growth factor receptor (EGFR), cyclin-dependent kinase inhibitors p21 and p27 were measured by western blots. Total and active forms of transforming growth factor (TGF)-β₁ were measured using ELISA and bioassay. TGF-β was inhibited using a recombinant TGF-β soluble receptor II protein.
Proliferation of epithelial cells from asthmatics (AE) is increased when cells were cultured with fibroblasts from normal controls (NF). Fibroblasts from asthmatics (AF) significantly decreased the proliferation of epithelial cells from healthy subjects (NE). Activation of p21, p27, EGFR and TGF-β₁ reflects the proliferation data by decreasing in AE cultured with NF and increasing in NE cultured with AF. Neutralization of TGF-β increased proliferation of epithelial cells cultured in the asthmatic model.
Fibroblasts from asthmatic subjects regulate epithelial cell prolifearation, and TGF-β signalling may represent one of the pathway involved in these interactions.
支气管上皮细胞被认为是协调气道壁重塑的关键因素。上皮细胞的功能可以通过基底成纤维细胞通过自分泌和旁分泌机制来调节。
研究哮喘患者支气管成纤维细胞表型变化对上皮细胞增殖的影响。
在工程模型中培养来自哮喘和健康对照者支气管活检的上皮细胞和成纤维细胞。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐（MTT）评估增殖。通过 Western blot 测量表皮生长因子受体（EGFR）、细胞周期蛋白依赖性激酶抑制剂 p21 和 p27。使用 ELISA 和生物测定法测量总转化生长因子（TGF）-β₁和活性形式。使用重组 TGF-β 可溶性受体 II 蛋白抑制 TGF-β。
当将上皮细胞与来自正常对照者（NF）的成纤维细胞共培养时，哮喘者（AE）的上皮细胞增殖增加。哮喘者（AF）的成纤维细胞显著降低了健康受试者（NE）的上皮细胞增殖。p21、p27、EGFR 和 TGF-β₁ 的激活反映了与 NF 共培养的 AE 中增殖数据的减少和与 AF 共培养的 NE 中增殖数据的增加。TGF-β 的中和增加了在哮喘模型中培养的上皮细胞的增殖。
哮喘患者的成纤维细胞调节上皮细胞增殖，TGF-β 信号可能代表这些相互作用中涉及的途径之一。
