Gene induction during differentiation of human pulmonary type II cells in vitro.

Wade KC, Guttentag SH, Gonzales LW, Maschhoff KL, Gonzales J, Kolla V, Singhal S, Ballard PL
Am J Respir Cell Mol Biol. 2006 34 (6): 727-37

PMID: 16474099 · PMCID: PMC2644235 · DOI:10.1165/rcmb.2004-0389OC

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 approximately 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.

MeSH Terms (23)

8-Bromo Cyclic Adenosine Monophosphate Cell Differentiation Cells, Cultured Dexamethasone Epithelial Cells Fatty Acid Synthases Fetal Proteins Fetus Gene Expression Profiling Gene Expression Regulation, Developmental Glycerol Kinase Humans Infant Infant, Newborn Lipoprotein Lipase Lung Lysosome-Associated Membrane Glycoproteins Phospholipids RNA, Messenger Subcellular Fractions Time Factors Transcriptional Activation Transferases (Other Substituted Phosphate Groups)

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