Trefoil Factor-2 Reverses Airway Remodeling Changes in Allergic Airways Disease
Trefoil Factor-2 Reverses Airway Remodeling Changes in Allergic Airways Disease
复制标题
DOI：
10.1165/rcmb.2011-0320oc
复制
发表时间：
2013-01-01
影响因子：
6.4
通讯作者：
Tang, Mimi L. K.
中科院分区：
文献类型：
--
作者：
Royce, Simon G.;Lim, Clarice;Tang, Mimi L. K.
三叶因子2(TFF2)是一种在粘膜修复中起重要作用的小肽。TFF2在哮喘中表达上调，提示TFF2在哮喘发病机制中发挥作用。鉴于其在促进上皮修复方面的已知生物学作用，TFF2有望在限制哮喘的气道重塑进展方面发挥保护作用。通过检测TFF2在哮喘小鼠气道和肺组织中的表达，以及评价重组TFF2治疗对慢性过敏性呼吸道疾病(AAD)小鼠已建立的气道重塑的影响，探讨TFF2在哮喘气道重塑中的作用。BALB/c小鼠用卵白蛋白(OVA)或生理盐水致敏并激发9周，而建立OVA诱导的AAD小鼠给予TFF2或赋形剂对照组(滴鼻14d)。然后评估对气道重塑、气道炎症和气道高反应性的影响，而TFF2的表达通过免疫组织化学方法测定。与对照组相比，AAD组小鼠呼吸道中TFF2的表达水平显著增加。TFF2治疗可减少上皮增厚、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(均P<；0.05，与赋形剂对照组相比)，但TFF2治疗不影响气道炎症。在慢性AAD小鼠模型中，内源性TFF2表达的增加对慢性变应性炎症的反应不足以阻止气道炎症和重塑的进展。然而，外源性TFF2治疗在逆转已建立的气道重塑方面是有效的。TFF2有可能成为治疗哮喘气道重塑的新药物。
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.