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Dexamethasone-induced prenatal alveolar wall thinning is associated with a decrease in EIIIA+ fibronectin isoform in

Hirokazu Arai1, Wataru Kikuchi, Akira Ishida

  • 1Department of Pediatrics, Akita University School of Medicine, Hondo 1-1-1, Akita, Akita 010-8543, Japan. arahiro@archosp-1998.com

Biology of the Neonate
|November 13, 2004
PubMed
Summary

Glucocorticoids, like dexamethasone, reduce EIIIA+ fibronectin (FN) and cell proliferation in fetal rat lungs. This suggests that altered EIIIA+ FN expression impacts lung development and cell growth.

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Area of Science:

  • Pulmonary medicine
  • Developmental biology
  • Molecular endocrinology

Background:

  • Glucocorticoid hormones are crucial for lung maturation, influencing architectural and biochemical development.
  • Glucocorticoids may indirectly affect lung development by modulating cell-matrix interactions, such as fibronectin (FN) expression.
  • Fibronectin (FN) exhibits various isoforms due to alternative splicing, with EIIIA being a key segment regulated during development.

Purpose of the Study:

  • To investigate the regulation of EIIIA-containing fibronectin (EIIIA+ FN) isoforms by glucocorticoids in the developing fetal rat lung.

Main Methods:

  • Pregnant rats were administered daily injections of dexamethasone (DEX) or saline from day 15 of gestation.
  • Fetal rat lungs were analyzed at day 20 of gestation (canalicular stage) for EIIIA+ FN and proliferating cell nuclear antigen (PCNA) expression.
  • Lung weight, septal wall thickness, and surfactant protein SP-B mRNA levels were assessed.

Main Results:

  • Dexamethasone treatment led to decreased fetal rat lung weight and reduced saccular septal wall thickness.
  • Surfactant protein SP-B mRNA expression was elevated in dexamethasone-treated lungs.
  • Expression of EIIIA+ fibronectin and PCNA around distal airspaces was significantly reduced in fetuses exposed to dexamethasone.

Conclusions:

  • Reduced EIIIA+ fibronectin expression in dexamethasone-treated lungs correlates with decreased pulmonary cell proliferation.
  • The findings suggest that glucocorticoid-induced changes in EIIIA+ fibronectin impact fetal lung cell proliferation.
  • EIIIA+ fibronectin may play a role in regulating the cell cycle during lung development.