Downregulation of epithelial sodium channel (ENaC) activity in cystic fibrosis cells by epigenetic targeting

• DOI: 10.1007/s00018-022-04190-9
• Publication Date: 2022-04-25T03:30:35Z
• Authors: Giovanna Blaconà; Roberto Raso; Stefano Castellani; Silvia Pierandrei; Paola Del Porto; Giampiero Ferraguti; Fiorentina Ascenz...; Massimo Conese; Marco Lucarelli
• Keywords: Epithelial sodium channel

Abstract The pathogenic mechanism of cystic fibrosis (CF) includes the functional interaction transmembrane conductance regulator (CFTR) protein with epithelial sodium channel (ENaC). reduction ENaC activity may constitute a therapeutic option for CF. This hypothesis was evaluated using drugs that target protease-dependent activation and transcriptional its coding genes. To this aim we used: camostat, protease inhibitor; S-adenosyl methionine (SAM), showed to induce DNA hypermethylation; curcumin, known produce chromatin condensation. SAM camostat are already clinically used in other pathologies, while curcumin is common dietary compound. experimental systems were CF non-CF immortalized human bronchial cell lines as well primary cells. SCNN1A , SCNN1B SCNN1G gene expression analyzed, addition promoter methylation. In both cells, inhibition extracellular peptidases epigenetic manipulations reduced activity. Notably, cells much more effective. appeared be best reduce activity, respect . Indeed, treatment resulted effective inducing hypermethylation lowering expression. Importantly, CFTR unaffected, or even upregulated, after treatments. These results open possibility patients’ by targeting.