Role of p63/p73 in epithelial remodeling and their response to steroid treatment in nasal polyposis

Background: Nasal polyposis (NP) is recognized as aberrant epithelial remodeling, but the molecular mechanism underlying this process is poorly understood. Two important p53 homologues (p63 and p73) play a key role in orchestrating the epithelial development. Objective: We intended to study whether p63 and p73 are involved in the epithelial remodeling seen in patients with NP and their response to oral glucocorticosteroid (GC) treatment. Methods: Nasal polyp tissues were obtained from 65 patients, and inferior turbinates were obtained from 19 control subjects without NP. Among patients with NP, 20 were treated with oral prednisone, so that 2 sets of polyp biopsy specimens were taken before (GC naive) and after (GC treated) treatment. Immunohistochemistry and quantitative PCR were performed to determine the expression levels of p63 and p73. Results: The increase in p63-positive cell numbers was significant in GC-naive NP epithelium (46%) compared with that seen in control epithelium (5%), and it was positively related to the epithelial hyperplasia in patients with NP. The increase in N-terminal transactivation domain p73-positive cell numbers was found in 27% of GC-naive patients with NP and 16% of control subjects, with no statistical difference. The mRNA expression of both p63 and p73 was significantly upregulated in GC-naive patients with NP versus control subjects, and a positive correlation between the p63 and p73 mRNAs was found in all nasal tissues. Furthermore, the improvement of epithelial structure and reduction of p63 mRNA/protein levels were found in patients with NP after GC treatment. Conclusions: Our results suggest that the ectopic expression of p63 in multiple cell layers is an important pathologic phenomenon in the epithelial remodeling seen in chronically inflamed airway epithelium (eg, in patients with NP), and its aberrant expression can be suppressed with GC treatment. (J Allergy Clin Immunol 2011;127:765-72.)