BioProject

The F508del mutation, the most frequent in cystic fibrosis (CF), impairs the maturation of the CFTR chloride channel. More...

The F508del mutation, the most frequent in cystic fibrosis (CF), impairs the maturation of the CFTR chloride channel. The F508del defect can be partially overcome at low temperature (27 °C) or with pharmacological correctors. The rescue elicited by low temperature may involve a direct stabilization of mutant CFTR protein and/or a change in cell transcriptome that creates a more favorable proteostasis environment. To assess the effect of low temperature on gene expression we investigated the transcriptome of bronchial epithelial cells derived from CF with F508del mutation. Cells were kept under control conditions or incubated at 27 °C. Microarray data indicate that hypothermia induces a profound and global change in gene expression that may be in part responsible for rescue of F508del-CFTR. Overall design: Bronchial epithelial cells from cystic fibrosis patients homozygotes for F508del mutation were isolated. Cells differentiated as epithelial monolayers on porous membranes (Snapwell inserts) were incubated for 24 hours at 27 °C or kept under control conditions. Rescue of mutant CFTR channel by low temperature was checked by measuring transepithelial chloride currents with the Ussing chamber technique. Total RNA was extracted from treated and control cells to assess changes in gene expression with microarrays. Less...