Dexamethasone-induced prenatal alveolar wall thinning is associated with a decrease in EIIIA+ fibronectin isoform in the fetal rat lung.
BACKGROUND
Glucocorticoid hormones play an important role in architectural and biochemical lung maturation. Although much of the molecular mechanism of their action in the lung is not fully understood, glucocorticoids directly or indirectly regulate lung maturation. Indirect effects of glucocorticoids may involve the modulation of cell-cell or cell-matrix interactions. Fibronectin (FN) is the major constituent of the pulmonary extracellular matrix and exists in multiple isoforms arising from alternative RNA splicing. EIIIA is the major alternatively spliced segment, and its expression is regulated in a spatiotemporal and oncodevelopmental manner.


OBJECTIVE
The present study focuses on the regulation of EIIIA-containing FN isoforms (referred to as EIIIA+ FN) by glucocorticoids in the developing lung.


METHODS
Dexamethasone (DEX) or saline was injected daily into pregnant rats from day 15 of gestation (term = day 22) until 24 h before sacrifice. The expression of EIIIA+ FN and proliferating cell nuclear antigen (PCNA), a biochemical marker for cell proliferation, was investigated in the fetal rat lung.


RESULTS
At day 20 of gestation (the canalicular stage), the DEX-treated lung showed a significant decrease in weight and saccular septal wall thickness, while the messenger RNA expression of the surfactant protein SP-B was increased in the DEX-treated lung, as compared with the control lung. The expression of EIIIA+ FN and PCNA around the distal airspaces was less extensive in the DEX-treated lung than in the control lung at day 20 of gestation.


CONCLUSIONS
Given the finding in vitro that EIIIA+ FN regulated the cell cycle, our results suggest that the change of EIIIA+ FN expression in the DEX-treated lung affected pulmonary cell proliferation.
Arai
Hirokazu
H
Department of Pediatrics, Akita University School of Medicine, Hondo 1-1-1, Akita, Akita 010-8543, Japan. arahiro@archosp-1998.com
Kikuchi
Wataru
W
Ishida
Akira
A
Takada
Goro
G
D017398:Alternative Splicing; D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005353:Fibronectins / Q000032:analysis / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D005865:Gestational Age; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry / Q000166:cytology / Q000196:embryology*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000196:embryology*; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D005353:Fibronectins; D005938:Glucocorticoids; D018809:Proliferating Cell Nuclear Antigen; D020033:Protein Isoforms; D037701:Pulmonary Surfactant-Associated Protein B; D012333:RNA, Messenger; D003907:Dexamethasone