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Epidermal growth factor strongly affects epithelial Na+ transport and barrier function in fetal alveolar cells, with

Mandy Laube1, Diana Dornis2, Fine Wenzel2

  • 1Department of Pediatrics, Division of Neonatology, Center for Pediatric Research Leipzig (CPL), University of Leipzig, Liebigstrasse 19, 04103, Leipzig, Germany. mandy.laube@medizin.uni-leipzig.de.

Scientific Reports
|August 6, 2021
PubMed

Insights

Epidermal growth factor (EGF) impacts fetal lung cells, reducing sodium transport channels. While EGF affects male and female cells differently, it is unlikely to be the cause of sex-specific differences in respiratory distress syndrome development.

Area of Science:

  • Neonatal Physiology
  • Pulmonary Medicine
  • Cellular Biology

Background:

  • Male sex is a risk factor for respiratory distress syndrome (RDS) in preterm infants.
  • Alveolar fluid clearance, dependent on sodium (Na+) transport, is crucial for preventing RDS.
  • Previous studies indicated sex-specific differences in Na+ transport and potential roles for epidermal growth factor (EGF) in lung development.

Purpose of the Study:

  • To investigate the sex-specific effects of EGF on Na+ transport in fetal distal lung epithelial (FDLE) cells.
  • To determine if EGF contributes to the sex-specific differences observed in RDS development.

Main Methods:

  • Primary fetal distal lung epithelial (FDLE) cells from male and female fetuses were cultured.
  • Cells were exposed to EGF and related ligands.
  • Na+ transport was measured using Ussing chambers.
  • Gene and protein expression of the epithelial Na+ channel (ENaC) and signaling pathways (AKT, pERK1/2) were analyzed via RT-qPCR and Western blots.

Main Results:

  • EGF significantly reduced ENaC mRNA levels and activity in both male and female FDLE cells.
  • Acute exposure to EGF reduced Na+ transport only in male FDLE cells.
  • EGF increased amiloride-insensitive pathways and improved barrier function.
  • Sex-specific signaling responses were observed: AKT phosphorylation increased only in females, while pERK1/2 increased in both sexes.

Conclusions:

  • EGF exerts sex- and time-dependent effects on Na+ transport and signaling in fetal lung epithelial cells.
  • Despite these effects, EGF is unlikely to be the primary cause of sex-specific differences in Na+ transport contributing to RDS.

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