[Antisense oligonucleotides for therapy of cystic fibrosis. Inhibition of sodium absorption mediated by ENaC in nasal epithelial cells]. / Antisense-Oligonukleotide zur Therapie der Mukoviszidose. Inhibition der ENaC-vermittelten Natriumabsorption in humanen Nasenepithelzellen.

BACKGROUND: The genetic disease cystic fibrosis (CF) is characterised by reduced chloride secretion mediated by the cystic fibrosis transmembrane conductance regulator (CFTR) and Na(+) hyperabsorption through amiloride-sensitive epithelial sodium channels (ENaC). Mutations in CFTR cause the accumulation of thick mucus and dysfunction of mucociliary clearance in the respiratory tract. MATERIAL AND METHODS: In this project it was investigated whether Na(+) hyperabsorption is inhibited by the use of antisense oligonucleotides (AON). For functional analyses monolayers of human non-CF and CF nasal epithelial cells were measured in modified Ussing chambers. To analyse the AON effects on the protein level Western blotting analyses were carried out. RESULTS: AON transfection significantly inhibits Na(+) absorption via ENaC in non-CF and CF cells. Furthermore, Western blot analyses demonstrate a suppression of the ENaC protein in AON transfected human non-CF cells. CONCLUSION: The inhibition of ENaC associated Na(+) absorption by specific AON could offer a new perspective for the regulation of the Na(+) hyperabsorption in CF patients.