RNA interference for CFTR attenuates lung fluid absorption at birth in rats.

RNA interference for CFTR attenuates lung fluid absorption at birth in rats.

Li T; Koshy S; Folkesson H G

Respiratory research

2008

2008-01

Background: Small interfering RNA (siRNA) against αENaC (α-subunit of the epithelial Na channel) and CFTR (cystic fibrosis transmembrane conductance regulator) was used to explore ENaC and CTFR function in newborn rat lungs. Methods: Twenty-four hours after trans-thoracic intrapulmonary (ttip) injection of siRNAgenerating plasmid DNA (pSi-0, pSi-4, or pSi-C2), we measured CFTR and ENaC expression, extravascular lung water, and mortality. Results: αENaC and CFTR mRNA and protein decreased by \textasciitilde80% and \textasciitilde85%, respectively, following αENaC and CFTR silencing. Extravascular lung water and mortality increased after αENaC and CFTR-silencing. In pSi-C2-transfected isolated DLE cells there were attenuated CFTR mRNA and protein. In pSi-4-transfected DLE cells αENaC mRNA and protein were both reduced. Interestingly, CFTR-silencing also reduced αENaC mRNA and protein. αENaC silencing, on the other hand, only slightly reduced CFTR mRNA and protein. Conclusion: Thus, ENaC and CFTR are both involved in the fluid secretion to absorption conversion around at birth.

Female; Pregnancy; Rats; Genes; Cells; Animal Population Groups; Animal Studies; Lung; Respiratory Mucosa; Genes – Drug Effects; Biological Transport – Drug Effects; Lung – Drug Effects; Lung – Metabolism; Membrane Proteins – Metabolism; Respiratory Mucosa – Drug Effects; Respiratory Mucosa – Metabolism; RNA – Metabolism; RNA – Pharmacodynamics; Water – Metabolism

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