Postnatal gene expression of airway epithelial sodium transporters associated with birth stress in humans

Pediatr Pulmonol. 2019 Jun;54(6):797-803. doi: 10.1002/ppul.24288. Epub 2019 Mar 28.

Abstract

Introduction: Lung fluid clearance is essential for successful postnatal pulmonary adaptation. The epithelial sodium channel (ENaC) and Na-K-ATPase, induced by serum- and glucocorticoid-inducible kinase 1 (SGK1) as well as aquaporins (AQP), represent key players in the switch from fetal lung fluid secretion to absorption and in early postnatal lung fluid balance. Birth stress, including a surge in catecholamines, promotes pulmonary adaptation, likely through the augmentation of epithelial sodium reabsorption.

Objectives: We sought to determine the changes in the airway gene expression of molecules vital to epithelial sodium transport during early pulmonary adaptation, and the association with birth stress reflected in the norepinephrine concentration in the cord blood in humans.

Methods: We included 70 term newborns: 28 born via vaginal delivery and 42 via elective cesarean section. We determined the norepinephrine concentrations in the cord blood using tandem mass spectrometry and collected nasal epithelial cell samples at 2 min, 1 h, and 24 h postnatally to quantify ENaC, Na-K-ATPase, AQP5, and SGK1 mRNAs using RT-PCR.

Results: The molecular gene expression involved in airway epithelium sodium transport changed markedly within the first hour postnatally. Newborns born via elective cesarean section exhibited a lower expression of ENaC, Na-K-ATPase, and SGK1. Significant correlations existed between the expressions of ENaC, Na-K-ATPase, and SGK1, and the concentration of norepinephrine in the cord blood.

Conclusions: The association of ENaC, Na-K-ATPase, and SGK1 expression with the cord blood norepinephrine concentration points to the importance of birth stress in promoting lung fluid clearance during early postnatal pulmonary adaptation.

Keywords: catecholamines; epithelial sodium channels; ion transport; newborn; norepinephrine; pulmonary adaptation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cesarean Section
  • Epithelial Cells / metabolism
  • Epithelial Sodium Channels / genetics*
  • Female
  • Fetal Blood / chemistry*
  • Gene Expression
  • Humans
  • Immediate-Early Proteins / genetics*
  • Infant, Newborn
  • Nasal Mucosa / cytology
  • Norepinephrine / blood*
  • Protein Serine-Threonine Kinases / genetics*
  • Sodium-Potassium-Exchanging ATPase / genetics*
  • Stress, Physiological / genetics*

Substances

  • Epithelial Sodium Channels
  • Immediate-Early Proteins
  • Protein Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase
  • Sodium-Potassium-Exchanging ATPase
  • Norepinephrine