Distinct Roles of FOXA2 and FOXA3 in Allergic Airway Disease and Asthma. Export

@article{citeulike:5286485, abstract = {RATIONALE: Increased production of mucus is a prominent feature of asthma. IL-13-driven mucous cell metaplasia is associated with decreased expression of the transcription factor FOXA2 and increased expression of the related transcription factor FOXA3 in animal and cell culture models. OBJECTIVES: Establish how changes in FOXA2 and FOXA3 expression contribute to mucous metaplasia and determine whether FOXA2 and FOXA3 expression is altered in asthma. METHODS: Mice expressing a Foxa2 transgene in airway epithelial cells and mice deficient in Foxa3 were analyzed after allergen sensitization and challenge. Expression of FOXA2, FOXA3, MUC5AC, and the highly IL-13-inducible gene CLCA1 was analyzed in airway biopsies from asthmatic and control subjects. MEASUREMENTS AND MAIN RESULTS: Expression of a Foxa2 transgene reduced allergen-induced mucous metaplasia by 45\% compared with control transgenic mice (P < 0.05) whereas inactivation of Foxa3 had no detectable effects on mucous metaplasia. Expression of FOXA2 was reduced in asthmatic subjects and was negatively correlated with MUC5AC and CLCA1 levels in asthmatics. In contrast, FOXA3 expression was not significantly correlated with MUC5AC and was positively correlated with CLCA1. CONCLUSIONS: Increasing Foxa2 expression reduced mucous metaplasia in an allergic mouse model. Asthmatics had decreased FOXA2 expression suggesting that therapeutic approaches that increase FOXA2 expression or function could be beneficial for reducing mucus production in asthma. Unlike FOXA2, FOXA3 did not regulate mucous metaplasia.}, author = {Park, Sung-Woo W. and Verhaeghe, Catherine and Nguyenvu, Louis T. and Barbeau, Rebecca and Eisley, Christopher J. and Nakagami, Yasuhiro and Huang, Xiaozhu and Woodruff, Prescott G. and Fahy, John V. and Erle, David J.}, citeulike-article-id = {5286485}, citeulike-linkout-0 = {http://dx.doi.org/10.1164/rccm.200811-1768OC}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19628779}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19628779}, day = {23}, doi = {10.1164/rccm.200811-1768OC}, issn = {1535-4970}, journal = {American journal of respiratory and critical care medicine}, keywords = {allergy, asthma, fox}, month = {July}, posted-at = {2009-07-28 04:39:59}, priority = {2}, title = {Distinct Roles of FOXA2 and FOXA3 in Allergic Airway Disease and Asthma.}, url = {http://dx.doi.org/10.1164/rccm.200811-1768OC}, year = {2009} }

TY - JOUR ID - citeulike:5286485 L3 - citeulike-article-id:5286485 N2 - RATIONALE: Increased production of mucus is a prominent feature of asthma. IL-13-driven mucous cell metaplasia is associated with decreased expression of the transcription factor FOXA2 and increased expression of the related transcription factor FOXA3 in animal and cell culture models. OBJECTIVES: Establish how changes in FOXA2 and FOXA3 expression contribute to mucous metaplasia and determine whether FOXA2 and FOXA3 expression is altered in asthma. METHODS: Mice expressing a Foxa2 transgene in airway epithelial cells and mice deficient in Foxa3 were analyzed after allergen sensitization and challenge. Expression of FOXA2, FOXA3, MUC5AC, and the highly IL-13-inducible gene CLCA1 was analyzed in airway biopsies from asthmatic and control subjects. MEASUREMENTS AND MAIN RESULTS: Expression of a Foxa2 transgene reduced allergen-induced mucous metaplasia by 45% compared with control transgenic mice (P < 0.05) whereas inactivation of Foxa3 had no detectable effects on mucous metaplasia. Expression of FOXA2 was reduced in asthmatic subjects and was negatively correlated with MUC5AC and CLCA1 levels in asthmatics. In contrast, FOXA3 expression was not significantly correlated with MUC5AC and was positively correlated with CLCA1. CONCLUSIONS: Increasing Foxa2 expression reduced mucous metaplasia in an allergic mouse model. Asthmatics had decreased FOXA2 expression suggesting that therapeutic approaches that increase FOXA2 expression or function could be beneficial for reducing mucus production in asthma. Unlike FOXA2, FOXA3 did not regulate mucous metaplasia. JF - American journal of respiratory and critical care medicine SN - 1535-4970 TI - Distinct Roles of FOXA2 and FOXA3 in Allergic Airway Disease and Asthma. KW - allergy KW - asthma KW - fox AU - Park, Sung-Woo AU - Verhaeghe, Catherine AU - Nguyenvu, Louis AU - Barbeau, Rebecca AU - Eisley, Christopher AU - Nakagami, Yasuhiro AU - Huang, Xiaozhu AU - Woodruff, Prescott AU - Fahy, John AU - Erle, David PY - 2009/07/23/ UR - http://dx.doi.org/10.1164/rccm.200811-1768OC ER -