Cell signaling and regulation of CFTR expression in cystic fibrosis cells in the era of high efficiency modulator therapy

Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP- and protein kinase A (PKA)-regulated channel, expressed on the luminal surface of secretory and absorptive epithelial cells. CFTR has a complex, cell-specific regulatory network playing a major role in cAMP- and Ca2+-activated secretion of electrolytes. It secretes intracellular Cl– and bicarbonate and regulates absorption of electrolytes by differentially controlling the activity of the epithelial Na+ channel (ENaC) in colon, airways, and sweat ducts. The CFTR gene expression is regulated by cell-specific, time-dependent mechanisms reviewed elsewhere [ [2] Ratjen F. Bell S.C. Rowe S.M. Goss C.H. Quittner A.L. Bush A. Cystic fibrosis. Nat Rev Dis Primers. 2015; 1: 15010https://doi.org/10.1038/nrdp.2015.10 Crossref PubMed Scopus (276) Google Scholar ]. This review will focus on the transcriptional, post-transcriptional, and translational regulation of CFTR by cAMP-PKA, non-coding (nc)RNAs, and TGF-β signaling pathways in cystic fibrosis (CF) cells.