Transcription factor p63 regulates differentiation- and repair-related genes in primary human bronchial epithelial cells: Implications for airway remodeling in asthma

Rationale: We have previously shown increased expression of the transcription factor p63 in the asthmatic epithelium, both in vivo and in vitro (Hackett et al. AJRCCM 2009 180(2):122-33). p63 is a crucial regulator of development and maintenance of a stratified epithelium in tissues such as the skin and kidney. Whether p63 has a similar role in regulating genes involved in airway epithelial barrier function, and could thus contribute to the airway remodeling seen in asthma, is unknown. Objective: To determine the role of p63 in regulating expression of genes involved in airway epithelial adhesion, differentiation, structural integrity and cell cycle progression. Methods: Monolayer cultures of primary human bronchial epithelial cells (n=5) were treated with 50nM custom Stealth siRNA (Invitrogen) targeting various p63 isoforms. RNA was collected at 48h and real-time qPCR for 21 epithelial genes was performed (SA Biosciences, USA). Results were normalized to GAPDH expression. One-way ANOVA with Dunnett9s post-test were employed to assess statistical significance. Results: Loss of p63 expression was found to significantly (p Conclusions: In primary human airway epithelial cells, p63 loss results in decreased expression of key genes involved in epithelial differentiation and repair. This may have an impact on the phenotype observed in the asthmatic epithelium.