RNA interference for CFTR attenuates lung fluid absorption at birth in rats
Small interfering RNA (siRNA) against alpha-ENaC (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: alpha-ENaC and CFTR mRNA and protein decreased by ~80% and ~85%, respectively, following alpha-ENaC and CFTR silencing. Extravascular lung water and mortality increased after alpha-ENaC and CFTR-silencing.
In pSi-C2-transfected isolated DLE cells there were attenuated CFTR mRNA and protein. In pSi-4-transfected DLE cells alpha-ENaC mRNA and protein were both reduced.
Interestingly, CFTR-silencing also reduced alpha-ENaC mRNA and protein. alpha-ENaC 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.
Author: Tianbo Li, Shyny Koshy and Hans G Folkesson
Credits/Source: Respiratory Research 2008, 9:55
Published on: 2008-07-24
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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