Does Arhgef7, a guanine nucleotide exchange factor, regulate epithelial sodium channel activity and lung aeration?

Abstract

Preterm infants have higher incidence of respiratory failure than term infants. These respiratory disorders are caused in part by delayed clearance of lung fluid. At birth, lung fluid clearance and aeration are mediated by active salt and water transport by epithelial sodium channel (ENaC) activity. Our lab has shown that oxidative environments can enhance ENaC activity, most likely via Nadph oxidase (Nox)‐mediated O2− release. In this highly regulated process, we have shown that the small G‐protein Rac1 plays an important role upstream of Nox signaling. However, the Rac1‐guanine nucleotide exchange factors (GEFs) involved in Nox‐mediated ENaC activity are unknown. Herein, we utilized quantitative real‐time PCR analysis to examine the expression profile of Rac1‐GEFs that may play an important role in ENaC regulation in the neonatal lung. Our major findings thus far are that transcript expression of Arhgef7>;>;>;Sos1>;Rasgrf2>;Tiam1>;Sos2, and that Arhgef7 transcript is expressed 1.5‐fold higher in neonatal (post‐partum day 7) mouse lung than adult mouse lung (n=8). This evidence suggests that Arhgef7 may play an integral role in neonatal lung aeration. Funding support: R00HL09226 awarded to MNH; Children's Center for Development in Lung Biology Grant awarded to MNH; and Emory University Summer Undergraduate Stipend awarded to DT.