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 Tianbo; Koshy Shyny; Folkesson Hans G

Respiratory research

2008

2008-07

BACKGROUND: Small interfering RNA (siRNA) against alphaENaC (alpha-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 siRNA-generating plasmid DNA (pSi-0, pSi-4, or pSi-C2), we measured CFTR and ENaC expression, extravascular lung water, and mortality. RESULTS: alphaENaC and CFTR mRNA and protein decreased by approximately 80% and approximately 85%, respectively, following alphaENaC and CFTR silencing. Extravascular lung water and mortality increased after alphaENaC and CFTR-silencing. In pSi-C2-transfected isolated DLE cells there were attenuated CFTR mRNA and protein. In pSi-4-transfected DLE cells alphaENaC mRNA and protein were both reduced. Interestingly, CFTR-silencing also reduced alphaENaC mRNA and protein. alphaENaC 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.

*RNA Interference; Animals; Biological Transport/drug effects; Cells; Cultured; Cystic Fibrosis Transmembrane Conductance Regulator/*genetics/*metabolism; Epithelial Sodium Channels/genetics/metabolism; Female; Gene Expression Regulation/drug effects; Lung/cytology/drug effects/*metabolism; Messenger/metabolism; Newborn; Pregnancy; Rats; Respiratory Mucosa/cytology/drug effects/metabolism; RNA; Small Interfering/*pharmacology; Sprague-Dawley; Water/*metabolism

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