SPDEF regulates goblet cell hyperplasia in the airway epithelium
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
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
View: Text | PDF
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

×

Figure 6

Conditional expression of SPDEF in vivo.

Options: View larger image (or click on image) Download as PowerPoint
Conditional expression of SPDEF in vivo. (A) Construct and strategy used...
(A) Construct and strategy used to express SPDEF in Clara cells in the conducting airway. (B) RT-PCR using primers that selectively detect transgenic Spdef mRNA revealed that transgene-specific Spdef mRNA was increased in whole lung in the presence, but not the absence, of doxycycline (Dox). GAPDH expression was detected as an internal control. (C–H) In situ hybridization (C and D) and immunostaining (G and H) were performed to detect the expression of Spdef mRNA and protein in conducting airways and lung parenchyma in the absence (C, E, and G) and the presence (D, F, and H) of doxycycline. (E and F) Serial sections from C and D were stained with hematoxylin and eosin. Spdef mRNA and protein were detected at the sites of goblet cell morphology in the conducting airways of CCSP-rtTA/TRE2-Spdef mice treated with doxycycline (arrows), but were not detected in the bronchiolar epithelium of the transgenic mice without doxycycline. Scale bars: 200 μm (C–F); 50 μm (G and H).