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Epidermal growth factor strongly affects epithelial Na⁺ transport and barrier function in fetal alveolar cells, with minor sex-specific effects.

ABSTRACT: Male sex remains an independent risk factor for respiratory distress syndrome (RDS) in preterm infants. Insufficient Na⁺ transport-mediated alveolar fluid clearance contributes to RDS development and we previously demonstrated sex-specific differences in Na⁺ transport. The epidermal growth factor (EGF) is important during fetal lung development with possible influence on Na⁺ transport. Sex-specific effects of EGF during surfactant synthesis were shown. We thus determined whether EGF exerts sex-specific effects on Na⁺ transport in fetal alveolar cells. We analyzed sex-specific fetal distal lung epithelial (FDLE) cells exposed to EGF and related ligands with Ussing chambers, RT-qPCR and Western blots. EGF strongly reduced the epithelial Na⁺ channel (ENaC) mRNA levels in both male and female FDLE cells. This was corroborated by a markedly reduced ENaC activity, while amiloride-insensitive pathways as well as barrier function were raised by EGF. In contrast to chronic effects, acute effects of EGF were sex-specific, because Na⁺ transport was reduced only in males. AKT phosphorylation was elevated only in female cells, while pERK1/2 was increased in both male and female cells. EGF showed certain sex- and time-dependent effects in FDLE cells. Nevertheless, the results suggest that EGF is an unlikely cause for the sex-specific differences in Na⁺ transport.

SUBMITTER: Laube M

PROVIDER: S-EPMC8342687 | biostudies-literature |

REPOSITORIES: biostudies-literature

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