Low Pulmonary Expression of Epithelial Na⁺ Channel and Na⁺, K⁺-ATPase in Newborn Infants with Congenital Diaphragmatic Hernia

Abstract

Background: It has been suggested from several animal studies and clinical observations that congenital diaphragmatic hernia (CDH) with pulmonary hypoplasia is accompanied by a disturbed perinatal ion transport. This could lead to respiratory distress due to slower clearance of fetal lung fluid at birth. Objectives: The purpose of this study was to determine whether CDH is related to changes in the expression of three rate-limiting transporter proteins in lung epithelium at birth. Methods: Tracheal aspirate was collected from 12 newborn infants with CDH and from 8 newborn control patients. Sampling was performed at postnatal age 18 and at 43 h in the CDH group and at 18 h in the control group. The protein abundance of α-, β- and γ-epithelial Na⁺ channel (ENaC), aquaporin 5 and Na⁺, K⁺-ATPase α₁ was analyzed using semiquantitative immunoblotting. Results: The levels of β-ENaC, γ-ENaC and Na⁺, K⁺-ATPase α₁ collected at 18 h postnatally were significantly lower in CDH infants compared to control infants. In the CDH group, no significant difference in the expression of the ENaC subunits, Na⁺, K⁺-ATPase α₁ or aquaporin 5 could be detected between the two sampling time points. Conclusions: This downregulation may result in an abnormal lung fluid absorption which could be an important mechanism behind the respiratory distress seen in newborn CDH patients.

Type I and II Pneumocyte Differentiation in the Developing Fetal Chicken Lung: Conservation of Pivotal Proteins from Birds to Human in the Struggle for Life at Birth

“…Prior to identification of Aqp5 and Cav1, few molecular markers were known for type I cells. Aqp5 is a transmembrane protein, expressed in type I cells of the human lung [18,19] and in some glands and the corneal epithelium of mammals. Aqp5 is a member of the aquaporin family, which includes important water transporter proteins.…”