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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/L1069    most recent 00151.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Li, T. Articles by Folkesson, H. G. Search for Related Content PubMed PubMed Citation Articles by Li, T. Articles by Folkesson, H. G.

Involvement of ENaC and Nedd4-2 in the conversion from lung fluid secretion to fluid absorption at birth in the rat as assayed by RNA interference analysis

Department of Physiology and Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio

Submitted 16 April 2007 ; accepted in final form 7 August 2007

To explore interactions between the epithelial Na channel (ENaC) and neural precursor expressed, developmentally downregulated protein 4-2 (Nedd4-2) at the conversion of the rat lung from fluid secretion to absorption at birth, we used small-interfering RNA (siRNA) against ENaC and Nedd4-2. siRNA-generating plasmid DNA (pDNA) was administered via trans-thoracic intrapulmonary (ttip) injection 24 h before ENaC and Nedd4-2 expression, extravascular lung water, and mortality were measured. ENaC mRNA and protein were specifically reduced by 65% after pSi-4 injection. Nedd4-2 mRNA and protein were reduced by 60% after pSi-N1 injection. Interestingly, ENaC and ENaC mRNA and protein expression were increased after Nedd4-2 silencing. Extravascular lung water was significantly increased after ENaC silencing and reduced after Nedd4-2 silencing. ENaC silencing resulted in a fourfold increase in newborn mortality, whereas silencing Nedd4-2 did not affect mortality. We also isolated distal lung epithelial (DLE) cells after in vivo ENaC or Nedd4-2 silencing and measured ENaC or Nedd4-2 expression in freshly isolated DLE cells. In these DLE cells, there were attenuated ENaC or Nedd4-2 mRNA and protein, thus demonstrating that ENaC and Nedd4-2 silencing occurred in alveolar epithelial cells after ttip injection. We also looked for pDNA by PCR to determine pDNA presence in the lungs and found strong evidence for pDNA presence in both lungs. Thus we provide evidence that ENaC and Nedd4-2 are involved in the transition from lung fluid secretion to fluid absorption near term and at birth.

distal lung epithelium; ion transport; lung development; newborn; ubiquitination

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