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

Tianbo Li , Shyny Koshy and Hans G Folkesson

Department of Integrative Medical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH 44272-0095, USA

author email corresponding author email

Respiratory Research 2008, 9:55doi:10.1186/1465-9921-9-55


Published:	24 July 2008

Abstract

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 siRNA-generating 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 ~80% and ~85%, 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.