Three conserved domains in the 3’UTR region of αENaC mRNA modulates the stability of the transcript in alveolar epithelial cells (716.1)

The epithelial sodium channel (ENaC) plays an important role in the alveolar epithelium by mediating Na+ reabsorption, an essential process for resolution of pulmonary edema in acute respiratory distress syndrome (ARDS). Several proinflammatory conditions such as TNF-α leads to a reduction of ENaC expression and activity that contributes to development of ARDS. To study how pro-inflammatory conditions could modulate αENaC mRNA stability, we developped a Tet-Off model that allows the specific inhibition of αENaC mRNA expression in presence of doxycycline. Using this model, we found that the half-life (T1/2) for the transcript was about 1 hr. TNF-α, a proinflammatory cytokine found in broncho-alveolar lavage of ARDS patients, decreased T1/2 to 15 min, suggesting that destabilisation of αENaC transcript plays an important role in downregulation of ENaC expression in pro-inflammatory conditions. The 3’ untranslated region (3’UTR) of a mRNA plays an important role in modulating mRNA stability. αENaC mRNA 3’UTR...