PT  - JOURNAL ARTICLE
AU  - Kimberley Wang
AU  - Timothy Le Cras
AU  - Alexander Larcombe
AU  - Graeme Zosky
AU  - Alan James
AU  - Peter Noble
TI  - Late-breaking abstract: Short-term, conditional TGFá expression produces airway smooth muscle thickening and hyperresponsiveness in mice deficient in early growth response one
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P4198
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P4198.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P4198.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Introduction: Expression of transforming growth factor alpha (TGFá) and its receptor, epidermal growth factor receptor, is increased in the airways of asthmatic patients. Mouse models show that prolonged TGFá expression promotes chronic lung disease particularly in early growth response-1 (Egr-1) deficient mice.Aim: To examine the role of short-term TGFá expression in airway disease including airway smooth muscle (ASM) thickening and airway responsiveness to methacholine (MCh).Method: TGFá was conditionally expressed in the airway epithelium of transgenic mice (Clara cell secretory protein-rtTA(+/-)/[tetO](7)-TGFá(+/-)) following 1W or 10d exposure to doxycycline in chow (Dox). Egr-1 deficient mice on Dox were compared with a control group that were wild type for Egr-1 and did not receive Dox. Airway and lung mechanics were assessed by the forced oscillation technique and lungs fixed for subsequent airway morphometry.Results: Mice exposed to Dox for 10d (n=8) produced thickening of the ASM layer compared with control (n=13) and an increase in airway responsiveness to MCh. Airway resistance was positively correlated to ASM layer thickness before (r=0.55, n=14) and after MCh (r=0.58, n=13). Shorter periods of Dox exposure (1W, n=7) had no effect on ASM layer thickness or airway responsiveness. Dox had no effect on tissue damping and lung elastance before or after MCh.Conclusion: Dox induced-TGFá expression in Egr-1 deficient mice, after 10d, produces thickening of the ASM layer, increased airway responsiveness, without a change in baseline lung mechanics. TGFá signalling may contribute to airway disease independent of inflammation.