Oxidative Stress RegulatesCFTRGene Expression in Human Airway Epithelial Cells through a Distal Antioxidant Response Element

• DOI: 10.1165/rcmb.2014-0263oc
• Publication Date: 2014-09-26T15:27:58Z
• Authors: Zhaolin Zhang; Shih-Hsing Leir; Ann Harris
• Keywords: 0303 health sciences; NF-E2-Related Factor 2; NF-kappa B; Cystic Fibrosis Transmembrane Conductance Regulator; Gene Expression; Bronchi; Epithelial Cells; MafK Transcription Factor; Antioxidant Response Elements; Fanconi Anemia Complementation Group Proteins; Cell Line; Oxidative Stress; 03 medical and health sciences; Basic-Leucine Zipper Transcription Factors; Enhancer Elements, Genetic; Mutagenesis, Site-Directed; Humans; Promoter Regions, Genetic; Transcription Factors

Cystic fibrosis transmembrane conductance regulator gene (CFTR) expression in human airway epithelial cells involves the recruitment of distal cis-regulatory elements, which are associated with airway-selective DNase hypersensitive sites at -44 kb and -35 from gene. The -35-kb site encompasses an enhancer that is regulated by immune mediators interferon regulatory factor 1 2 nuclear Y. Here we investigate -44-kb element, also has activity vitro but inactive intestinal cells. This contains antioxidant response element (ARE) plays a critical role its function cell lines primary bronchial natural sulforaphane (SFN) induces translocation factor, erythroid 2-like (Nrf2), transcription regulates genes AREs their promoters, many involved to injury. Under normal conditions, ARE occupied repressor BTB CNC homology 1, basic leucine zipper (Bach1), v-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog K (MafK) heterodimers. After hours SFN treatment, Nrf2 displaces these repressive factors activates CFTR expression. Site-directed mutagenesis shows both adjacent NF-κB binding required for activation Moreover, this functionally linked modulating environmental stresses airway.