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


CONCLUSIONS
Thus, ENaC and CFTR are both involved in the fluid secretion to absorption conversion around at birth.
Li
Tianbo
T
Department of Integrative Medical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH 44272-0095, USA. Tianbo.Li@yale.edu
Koshy
Shyny
S
Folkesson
Hans G
HG
D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014867:Water / Q000378:metabolism*
D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C440894:Scnn1a protein, rat; D014867:Water; D019005:Cystic Fibrosis Transmembrane Conductance Regulator