Induced trefoil factor family 1 expression by trans-differentiating Clara cells in a murine asthma model
Induced trefoil factor family 1 expression by trans-differentiating Clara cells in a murine asthma model
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DOI：
10.1165/rcmb.2006-0008oc
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发表时间：
2007-03-01
影响因子：
6.4
通讯作者：
Hoffmann, Werner
中科院分区：
文献类型：
--
作者：
Kouznetsova, Irina;Chwieralski, Caroline E.;Hoffmann, Werner
哮喘是一种慢性气道炎症性疾病，伴有杯状细胞化生和粘液分泌过多。三叶因子家族 (TFF) 肽是呼吸道的主要分泌产物，与粘蛋白一起合成。在小鼠肺中，TFF2 主要表达，而 TFF1 转录物仅代表少数物种。 TFF 肽以其促运动和抗凋亡作用而闻名，它们可调节支气管上皮细胞的炎症反应。在此，研究了已建立的哮喘小鼠模型（即暴露于烟曲霉 [AF] 抗原）。肺组织的 RT-PCR 分析显示，在 AF 致敏/攻击的动物中，尤其是 TFF I 转录物的水平升高。相比之下，编码 Clara 细胞分泌蛋白 (CCSP/CC10) 的转录本在这些动物中明显减少。为了进行比较，监测了杯状细胞分泌颗粒标记物 mCLCA3/Gob-5、粘蛋白 Muc1-Muc6 和 Muc19、分泌球蛋白 ScgB3A1 和 ScgB3A2 以及哺乳动物室管膜相关基因 MERP2 的表达。免疫组织化学将 TFF1 主要定位于具有混合表型的细胞中（例如，TFF1 阳性细胞用凝集素麦芽凝集素 (WGA) 染色，可识别杯状细胞特有的粘蛋白）。此外，这些细胞还表达 Clara 细胞标记物 CCSP/CC10。与粘蛋白或 CCSP/CC10 相比，TFF1 储存在位于这些细胞更基底外侧部分的不同分泌颗粒群中。因此，结果首次表明过敏原暴露导致 Clara 细胞向表达 TFF1 的粘液表型转分化。
Asthma is a chronic inflammatory disease of the airways that is accompanied by goblet cell metaplasia and mucus hypersecretion. Trefoil factor family (TFF) peptides represent major secretory products of the respiratory tract and are synthesized together with mucins. In the murine lung, TFF2 is mainly expressed, whereas TFF1 transcripts represent only a minor species. TFF peptides are well known for their motogenic and anti-apoptotic effects, and they modulate the inflammatory response of bronchial epithelial cells. Here, an established mouse model of asthma was investigated (i.e., exposure to Aspergillus fumigatus [AF] antigens). RT-PCR analysis of lung tissue showed elevated levels particularly of TFF I transcripts in AF-sensitized/challenged animals. In contrast, transcripts encoding Clara cell secretory protein (CCSP/CC10) were strongly diminished in these animals. For comparison, the expression of the goblet cell secretory granule marker mCLCA3/Gob-5, the mucins Muc1-Muc6 and Muc19, and the secretoglobins ScgB3A1 and ScgB3A2, as well as the mammalian ependymin-related gene MERP2, were monitored. Immunohistochemistry localized TFF1 mainly in cells with a mixed phenotype (e.g., TFF1-positive cells stain with the lectin wheat germ agglutinin (WGA), which recognizes mucins characteristic of goblet cells). In addition, these cells express CCSP/CC10, a Clara cell marker. When compared with mucins or CCSP/CC10, TFF1 was stored in a different population of secretory granules localized at the more basolateral portion of these cells. Thus, the results presented indicate for the first time that allergen exposure leads to the trans-differentiation of Clara cells toward a TFF1-expressing mucous phenotype.