Royce Simon G, Tan Liling, Koek Alicia A, Tang Mimi L K
Department of Allergy and Immunology, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
Ann Allergy Asthma Immunol. 2009 Mar;102(3):238-46. doi: 10.1016/S1081-1206(10)60087-7.
Airway remodeling in asthma is characterized by structural changes to the airways including extracellular matrix (ECM) deposition and epithelial metaplasia. Extracellular matrix deposition in the subepithelial region may play an important role in modulation of epithelial cell and fibroblast structure and function because it lies in immediate contact with these cell types and exists within the functional epithelial mesenchymal trophic unit.
To investigate the effect of aberrant ECM components on airway epithelial cells and fibroblasts and the relationship among subepithelial ECM deposition, other remodeling changes, and airway hyperresponsiveness.
BEAS-2B human airway epithelial cells and WI-38 human airway fibroblast cells were cultured on various ECM protein substrates (Matrigel, representing normal basement membrane matrix, or aberrant matrix proteins collagen I, collagen III, and fibronectin). Airway remodeling changes were determined using morphometry in sections from a murine model of chronic allergic airway disease. Airway reactivity to methacholine was determined, and these parameters correlated.
Abnormal ECM substrates induced epithelial and fibroblast proliferation and altered the cell morphology of both human airway epithelial cells and fibroblasts when compared with normal basement membrane ECM. Subepithelial matrix deposition in the mouse correlated with epithelial thickness, but only weak correlations were noted among the other parameters.
We have demonstrated that ECM may affect the growth of airway epithelial cells and fibroblasts in vitro and may influence epithelial thickness in the mouse. These findings may have implications for understanding the pathogenesis of asthma and future therapeutic targeting of airway remodeling.
哮喘中的气道重塑以气道的结构变化为特征，包括细胞外基质（ECM）沉积和上皮化生。上皮下区域的细胞外基质沉积可能在调节上皮细胞和成纤维细胞的结构与功能中起重要作用，因为它与这些细胞类型直接接触并存在于功能性上皮-间充质营养单位内。
研究异常的细胞外基质成分对气道上皮细胞和成纤维细胞的影响，以及上皮下细胞外基质沉积、其他重塑变化与气道高反应性之间的关系。
将BEAS-2B人气道上皮细胞和WI-38人气道成纤维细胞培养在各种细胞外基质蛋白底物上（基质胶，代表正常基底膜基质，或异常基质蛋白I型胶原、III型胶原和纤连蛋白）。使用慢性过敏性气道疾病小鼠模型切片的形态计量学来确定气道重塑变化。测定气道对乙酰甲胆碱的反应性，并对这些参数进行相关性分析。
与正常基底膜细胞外基质相比，异常的细胞外基质底物诱导上皮细胞和成纤维细胞增殖，并改变了人气道上皮细胞和成纤维细胞的细胞形态。小鼠上皮下基质沉积与上皮厚度相关，但在其他参数之间仅观察到弱相关性。
我们已经证明，细胞外基质可能在体外影响气道上皮细胞和成纤维细胞的生长，并可能影响小鼠的上皮厚度。这些发现可能对理解哮喘的发病机制以及未来气道重塑的治疗靶点具有重要意义。
