HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 24/2/105    most recent 00148.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Sozo, F. Articles by Hooper, S. B. Search for Related Content PubMed PubMed Citation Articles by Sozo, F. Articles by Hooper, S. B.

Gene expression profiling during increased fetal lung expansion identifies genes likely to regulate development of the distal airways

Department of Physiology, Monash University, Melbourne, Australia

Growth and development of the fetal lungs is critically dependent on the degree to which the lungs are expanded by liquid; increases in fetal lung expansion accelerate lung growth, whereas reductions in lung expansion cause lung growth to cease. The mechanisms mediating expansion-induced lung growth are unknown but likely include alterations in the expression of genes that regulate lung cell proliferation. Our aim was to isolate and identify genes that are up- or downregulated by increased fetal lung expansion. In chronically catheterized fetal sheep at 126 days gestational age (GA), the left lung was expanded for 36 h, while the right lung remained at a control level of expansion. Subtraction hybridization was used to isolate genes differentially expressed between the left and right lungs. Screening of 6,000 clones identified 1,138 and 118 cDNA fragments that were up- and downregulated by increased lung expansion, respectively. Northern blot analyses in separate groups of control fetuses and fetuses exposed to increased lung expansion were used to verify differential expression. Increased fetal lung expansion upregulated heat shock protein 47, thrombospondin-1, TROP2, tropoelastin, and tubulin-3 in fetal lung tissue by 200–300%; connective tissue growth factor and cysteine-rich angiogenic inducer 61 were increased by 20–30%. Genes downregulated by increased fetal lung expansion included CCSP-related protein-1, elongation factor-1 and vitamin D₃ upregulated protein 1. We conclude that an increase in fetal lung expansion differentially regulates the expression of numerous genes in lung tissue, many of which have important putative roles in lung development, while the functions of others are currently unknown.

lung development; subtraction hybridization; gene array; sheep; fetus

This article has been cited by other articles:

				F. Sozo, S. B. Hooper, and M. J. Wallace Thrombospondin-1 expression and localization in the developing ovine lung J. Physiol., October 15, 2007; 584(2): 625 - 635. [Abstract] [Full Text] [PDF]

				D. Warburton and V. Kaartinen When the lung is stretched, could it be thrombospondin via TGFbeta1 peptide activation? J. Physiol., October 15, 2007; 584(2): 365 - 365. [Full Text] [PDF]

				J. R. Bourbon and A. Benachi CFTR gene therapy, a method to rescue lung hypoplasia in congenital diaphragmatic hernia? Am J Physiol Lung Cell Mol Physiol, July 1, 2006; 291(1): L1 - L3. [Full Text] [PDF]