Published ahead of print on February 10, 2006, doi:10.1165/rcmb.2004-0389OC
© 2006 American Thoracic Society DOI: 10.1165/rcmb.2004-0389OC Gene Induction during Differentiation of Human Pulmonary Type II Cells In VitroDepartment of Pediatrics, Division of Neonatology, the Children's Hospital of Philadelphia; and Section of Thoracic Surgery, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Correspondence and requests for reprints should be addressed to Philip L. Ballard, M.D., Ph.D., Children's Hospital of Philadelphia, 416 Abramson Research Center, 3516 Civic Center Boulevard, Philadelphia, PA. E-mail: ballardp{at}email.chop.edu
Mature alveolar type II cells that produce pulmonary surfactant are essential for adaptation to extrauterine life. We profiled gene expression in human fetal lung epithelial cells cultured in serum-free medium containing dexamethasone and cyclic AMP, a treatment that induces differentiation of type II cells. Microarray analysis identified 388 genes that were induced > 1.5-fold by 72 h of hormone treatment. Induced genes represented all categories of molecular function and subcellular location, with increased frequency in the categories of ionic channel, cell adhesion, surface film, lysosome, extracellular matrix, and basement membrane. In time-course experiments, self-organizing map analysis identified a cluster of 17 genes that were slowly but highly induced (5- to
Key Words: cyclic AMP • epithelial differentiation • glucocorticoid • human fetal lung • type II cell This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
190-fold) and represented four functional categories: surfactant-related (SFTPC, SFTPA, PGC, SFTPB, LAMP3, LPL), regulatory (WIF2, IGF2, IL1RL1, NR4A2, HIF3A), metabolic (MAOA, ADH1B, SEPP1), and transport (SCNN1A, CLDN18, AQP4). Induction of both mRNA and protein for these genes, which included nine newly identified regulated genes, was confirmed, and cellular localization was determined in both fetal and postnatal tissue. Induction of lysosomal-associated membrane protein 3 required both hormones, and expression was localized to limiting membranes of lamellar bodies. Hormone-induced differentiation of human type II cells is associated with genome-wide increased expression of genes with diverse functions. 
