SPDEF regulates goblet cell hyperplasia in the airway epithelium
SPDEF regulates goblet cell hyperplasia in the airway epithelium
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DOI：
10.1172/jci29176
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发表时间：
2007-04-01
影响因子：
15.9
通讯作者：
Whitsett, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Park, Kwon-Sik;Korfhagen, Thomas R.;Whitsett, Jeffrey A.
杯状细胞增生和粘液分泌过多是慢性肺疾病包括囊性纤维化、哮喘和慢性阻塞性肺疾病的发病机制。在本工作中，小鼠SAM指向域的ETS转录因子（SPDEF）的mRNA和蛋白质的气管，支气管和气管腺内衬上皮细胞的子集进行了检测。SPDEF与甲状腺转录因子1的C-末端结构域相互作用，激活气道上皮细胞中选择性表达的基因的转录，包括Sftpa、Scgb 1a 1、Foxj 1和Sox 17。成年转基因小鼠呼吸道上皮中Spdef的表达引起杯状细胞增生，在体内诱导酸性和中性粘蛋白，并在体内对酸性和中性粘蛋白进行染色。在IL-13和尘螨变应原引起的杯状细胞增生部位，SPDEF表达增加，这一过程依赖于STAT-6。SPDEF在鼻内过敏原暴露和Th 2细胞因子刺激后诱导，并且足以引起Clara细胞在体内的杯状细胞分化。
Goblet cell hyperplasia and mucous hypersecretion contribute to the pathogenesis of chronic pulmonary diseases including cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In the present work, mouse SAM pointed domain-containing ETS transcription factor (SPDEF) mRNA and protein were detected in subsets of epithelial cells lining the trachea, bronchi, and tracheal glands. SPDEF interacted with the C-terminal domain of thyroid transcription factor 1, activating transcription of genes expressed selectively in airway epithelial cells, including Sftpa, Scgb1a1, Foxj1, and Sox17. Expression of Spdef in the respiratory epithelium of adult transgenic mice caused goblet cell hyperplasia, inducing both acidic and neutral mucins in vivo, and stainined for both acidic and neutral mucins in vivo. SPDEF expression was increased at sites of goblet cell hyperplasia caused by IL-13 and dust mite allergen in a process that was dependent upon STAT-6. SPDEF was induced following intratracheal allergen exposure and after Th2 cytokine stimulation and was sufficient to cause goblet cell differentiation of Clara cells in vivo.