SPDEF regulates goblet cell hyperplasia in the airway epithelium
Kwon-Sik Park, … , Gang Chen, Jeffrey A. Whitsett
Kwon-Sik Park, … , Gang Chen, Jeffrey A. Whitsett
Published April 2, 2007
Citation Information: J Clin Invest. 2007;117(4):978-988. https://doi.org/10.1172/JCI29176.
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Research Article Pulmonology

SPDEF regulates goblet cell hyperplasia in the airway epithelium

Abstract

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.

Authors

Kwon-Sik Park, Thomas R. Korfhagen, Michael D. Bruno, Joseph A. Kitzmiller, Huajing Wan, Susan E. Wert, Gurjit K. Khurana Hershey, Gang Chen, Jeffrey A. Whitsett

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Figure 8

Morphometric analysis of goblet cell hyperplasia.

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Morphometric analysis of goblet cell hyperplasia. (A) Alcian blue staini...
(A) Alcian blue staining (μm2/mm) was increased significantly in CCSP-rtTA/TRE2-Spdef mice exposed to doxycycline compared with unexposed mice (P = 0.004; Kruskal-Wallis 1-way ANOVA on ranks). Staining was increased in all 4 categories of airways: cartilagenous, proximal (noncartilagenous), central, and distal. Pairwise comparisons of the data for the 4 different airway categories demonstrated that the increase in Alcian blue staining was most significant in the proximal airways of the doxycycline-exposed double-transgenic mice. *P = 0.026; Mann-Whitney rank-sum test. (B) Alcian blue staining was observed only in airways associated with cartilage, not in the epithelia of noncartilagenous airways, in double-transgenic mice without doxycycline. (C) Alcian blue staining was observed in epithelial cells lining these regions conducting airways in the presence of doxycycline. (D) Minimal SPDEF staining was observed in control mice at this antibody dilution. (E) Increased staining for SPDEF was observed in conducting airways of doxycycline-exposed double-transgenic mice. Scale bars: 500 μm.