SPDEF regulates goblet cell hyperplasia in the airway epithelium

• Published in: The Journal of clinical investigation Vol. 117; no. 4; pp. 978 - 988
• Main Authors: Park, Kwon-Sik, Korfhagen, Thomas R, Bruno, Michael D, Kitzmiller, Joseph A, Wan, Huajing, Wert, Susan E, Khurana Hershey, Gurjit K, Chen, Gang, Whitsett, Jeffrey A
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01-04-2007
• Subjects: Animals; Binding Sites; Biomedical research; Cell Differentiation; Cell Line; Cytokines - physiology; Dermatophagoides; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; Gene expression; Gene Expression Regulation; Genetic Variation; Goblet Cells - cytology; Goblet Cells - physiology; History, 16th Century; Humans; Hyperplasia; Hyperplasia - physiopathology; Lung - growth & development; Lung - physiology; Lung Neoplasms; Mice; Proto-Oncogene Proteins c-ets - genetics; Proto-Oncogene Proteins c-ets - metabolism; Proto-Oncogene Proteins c-ets - physiology; Respiratory Mucosa - pathology; Respiratory Mucosa - physiology; Respiratory Mucosa - physiopathology; RNA, Messenger - genetics; Th2 Cells - physiology; Trachea; Trachea - physiology; Transcription Factors; Transcription, Genetic; United States
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI29176

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.