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Oral steroids enhance epithelial repair in nasal polyposis via up-regulation of AP-1 gene network
  1. Chun Wei Li (lichunwei{at}nus.edu.sg)
  1. National University of Singapore, Singapore
    1. Wai Cheung
    1. Department of Pediatrics, University of California San Diego, United States
      1. Zhi Bin Lin
      1. Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yet-Sent University, China
        1. Tian Ying Li
        1. Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yet-Sent University, China
          1. Joe Thuan Lim
          1. Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
            1. De Yun Wang (entwdy{at}nus.edu.sg)
            1. Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

              Abstract

              Background: Chronic mucosal inflammation, epithelial damage and aberrant tissue remodeling are common features in nasal polyposis (NP). We sought to characterize gene expression profile within NP tissues and to explore the molecular mechanisms underlying the ameliorative effects of glucocorticosteroids (GCs) in NP.

              Methods: Two sets of NP biopsies, i.e., before the initiation and after GC treatment, were taken from 10 patients with untreated (GC-naïve) bilateral NP. Biopsy of inferior turbinate from 6 patients who underwent surgery for nasal septal deviation was served as nasal mucosal control. DNA microarrays containing 38,500 genes were used to characterize global gene expression profile. Functional network analysis was applied to identify key molecular pathways and genes in response to GC treatment (GC-treated). Selected genes were retested by means of quantitative RT-PCR and immunohistochemistry in the same polyps and control samples.

              Results: Sixty-four genes were differentially expressed in GC-treated versus GC-naïve NP tissues. Highest scoring network was assembled around activation protein 1 (AP-1), a heterodimer of c-Fos and c-Jun oncoprotein, and 5 AP-1 related genes (COX-2, IL-6, AREG, HBEGF and EGR1) with tissue repair function. Quantitative PCR confirmed that AP-1 and its related genes were markedly repressed in GC-naïve polyps and were up-regulated after GC treatment. Immunohistochemical staining indicated that epithelial restitution in GC-treated polyps were associated with elevated expression of c-Jun protein.

              Conclusions: This study demonstrates oral steroids promote epithelial repair in NP via up-regulation of AP-1 (especially c-Jun) network and its related genes.

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