Gata5 Deficiency Causes Airway Constrictor Hyperresponsiveness in Mice
Year: 2013
Type: article
Abstract: Gata5 is a transcription factor expressed in the lung, but its physiological role is unknown. To test whether and how Gata5 regulates airway constrictor responsiveness, we studied Gata5(-/-), Gata5(+/-), and wild-type mice on the C57BL/6J background. Cholinergic airway constrictor responsiveness was assessed invasively in mice without and with induction of allergic airway inflammation through ovalbumin sensitization and aerosol exposure. Gata5-deficient mice displayed native airway constrictor hyperresponsiveness (AHR) in the absence of allergen-induced inflammation. Gata5-deficient mice retained their relatively greater constrictor responsiveness even in ovalbumin-induced experimental asthma. Gata5 deficiency did not alter the distribution of cell types in bronchoalveolar lavage fluid, but bronchial epithelial mucus metaplasia was more prominent in Gata5(-/-) mice after allergen challenge. Gene expression profiles revealed that apolipoprotein E (apoE) was the fifth most down-regulated transcript in Gata5-deficient lungs, and quantitative RT-PCR and immunostaining confirmed reduced apoE expression in Gata5(-/-) mice. Quantitative RT-PCR also revealed increased IL-13 mRNA in the lungs of Gata5-deficient mice. These findings for the first time show that Gata5 regulates apoE and IL-13 expression in vivo and that its deletion causes AHR. Gata5-deficient mice exhibit an airway phenotype that closely resembles that previously reported for apoE(-/-) mice: both exhibit cholinergic AHR in native and experimental asthma states, and there is excessive goblet cell metaplasia after allergen sensitization and challenge. The Gata5-deficient phenotype also shares features that were previously reported for IL-13-treated mice. Together, these results indicate that Gata5 deficiency induces AHR, at least in part, by blunting apoE and increasing IL-13 expression.
Authors: Bohao Chen, Tamson V. Moore, Zhenping Li, Anne I. Sperling, Chunling Zhang, Jorge Andrade, Alex Rodriguez, Neil Bahroos, Yong Huang, Edward E. Morrisey, Peter J. Gruber, Julian Solway
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: The Role of GATA6 in Lung Development, SCOR in Cellular and Molecular Mechanisms of Asthma, Re-Engineering Translational Research at the University of Chicago, Airway inflammation and HLA-G in asthma, Multidisciplinary Research Training in Asthma Genetics & Genomics, Epigenic Regulation of Lung Progenitor Repair and Regeneration, Interdisciplinary Training Program in Immunology
OpenAlex ID: W2023937509