Lung retinol storing cells synthesize and secrete retinoic acid, an inducer of alveolus formation.
Retinoids play a key role in the formation of pulmonary alveoli. Lipid interstitial cells (LICs) of the alveolar wall store retinol and are concentrated at sites of alveolus formation, suggesting they are an endogenous source of retinoids for alveolus formation. We show in cultured rat lung cells that LICs synthesize and secrete all-trans retinoic acid (ATRA); its secretion is halved by dexamethasone, an inhibitor of alveolus formation. In a second alveolar wall cell, the pulmonary microvascular endothelial cell (PMVC), ATRA increases expression of the mRNA of cellular retinol binding protein-I (CRBP-I), a protein involved in ATRA synthesis. Serum-free, exogenous ATRA-free medium conditioned by LICs rich in retinol storage granules caused a 10-fold greater increase of CRBP-I mRNA in PMVCs than media conditioned by LICs with few retinol storage granules. This action of medium conditioned by retinol storage granule-rich LICs is decreased by a retinoic acid receptor pan-antagonist and by a retinoid X receptor pan-antagonist, suggesting the responsible molecule(s) is a retinoid and that retinoid signaling occurs in a paracrine fashion.
Dirami
Ghenima
G
Lung Biology Laboratory, Box 571481, Department of Medicine, Georgetown University School of Medicine, 3900 Reservoir Rd., NW, Washington, DC 20057-1481, USA.
Massaro
Gloria DeCarlo
GD
Clerch
Linda Biadasz
LB
Ryan
Una S
US
Reczek
Peter R
PR
Massaro
Donald
D
D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000196:embryology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005938:Glucocorticoids / Q000494:pharmacology; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D047488:Retinoid X Receptors; D012177:Retinol-Binding Proteins / Q000235:genetics; D054840:Retinol-Binding Proteins, Cellular; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*; D014801:Vitamin A / Q000378:metabolism*
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D005938:Glucocorticoids; D012333:RNA, Messenger; C518458:Rbp1 protein, rat; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D014157:Transcription Factors; D014801:Vitamin A; D014212:Tretinoin; D003907:Dexamethasone