Department of Allergy and Immune Disorders, Murdoch Children's Research Institute Melbourne, Victoria, Australia.
Am J Respir Cell Mol Biol. 2013 Jan;48(1):135-44. doi: 10.1165/rcmb.2011-0320OC. Epub 2012 May 31.
Trefoil factor 2 (TFF2) is a small peptide with an important role in mucosal repair. TFF2 is up-regulated in asthma, suggesting a role in asthma pathogenesis. Given its known biological role in promoting epithelial repair, TFF2 might be expected to exert a protective function in limiting the progression of airway remodeling in asthma. The contribution of TFF2 to airway remodeling in asthma was investigated by examining the expression of TFF2 in the airway and lung, and evaluating the effects of recombinant TFF2 treatment on established airway remodeling in a murine model of chronic allergic airways disease (AAD). BALB/c mice were sensitized and challenged with ovalbumin (OVA) or saline for 9 weeks, whereas mice with established OVA-induced AAD were treated with TFF2 or vehicle control (intranasally for 14 d). Effects on airway remodeling, airway inflammation, and airway hyperresponsiveness were then assessed, whereas TFF2 expression was determined by immunohistochemistry. TFF2 expression was significantly increased in the airways of mice with AAD, compared with expression levels in control mice. TFF2 treatment resulted in reduced epithelial thickening, subepithelial collagen deposition, goblet-cell metaplasia, bronchial epithelium apoptosis, and airway hyperresponsiveness (all P < 0.05, versus vehicle control), but TFF2 treatment did not influence airway inflammation. The increased expression of endogenous TFF2 in response to chronic allergic inflammation is insufficient to prevent the progression of airway inflammation and remodeling in a murine model of chronic AAD. However, exogenous TFF2 treatment is effective in reversing aspects of established airway remodeling. TFF2 has potential as a novel treatment for airway remodeling in asthma.
三叶因子 2（TFF2）是一种在黏膜修复中具有重要作用的小肽。TFF2 在哮喘中上调，提示其在哮喘发病机制中起作用。鉴于其已知的促进上皮修复的生物学作用，TFF2 可能在限制哮喘气道重塑的进展中发挥保护作用。通过检查 TFF2 在气道和肺中的表达，并评估重组 TFF2 治疗对慢性变应性气道疾病（AAD）小鼠模型中已建立的气道重塑的影响，研究了 TFF2 对哮喘气道重塑的贡献。BALB/c 小鼠用卵清蛋白（OVA）或生理盐水致敏和激发 9 周，而已经建立的 OVA 诱导的 AAD 小鼠用 TFF2 或载体对照（鼻腔内）治疗 14 d。然后评估对气道重塑、气道炎症和气道高反应性的影响，同时通过免疫组织化学法确定 TFF2 的表达。与对照小鼠相比，AAD 小鼠气道中 TFF2 的表达显著增加。TFF2 治疗导致上皮增厚、上皮下胶原沉积、杯状细胞化生、支气管上皮细胞凋亡和气道高反应性降低（均 P < 0.05，与载体对照相比），但 TFF2 治疗不影响气道炎症。内源性 TFF2 在慢性变应性炎症中的表达增加不足以防止慢性 AAD 小鼠模型中气道炎症和重塑的进展。然而，外源性 TFF2 治疗可有效逆转已建立的气道重塑的某些方面。TFF2 有潜力成为哮喘气道重塑的新治疗方法。
