|
|
||||||||
1 Lung Biology Program, Hospital for Sick Children Research Institute, 2 Thoracic Surgery Research Laboratory, The Toronto Hospital Research Institute, and Departments of 5 Paediatrics, 6 Physiology, 4 Medicine, and 3 Surgery, University of Toronto, Toronto, Ontario, Canada M5G 1X8
Physical forces derived from fetal breathing movements and hormones such as glucocorticoids are implicated in regulating fetal lung development. To elucidate whether the different signaling pathways activated by physical and hormonal factors are integrated and coordinated at the cellular and transcriptional levels, organotypic cultures of mixed fetal rat lung cells were subjected to static culture or mechanical strain in the presence and absence of dexamethasone. Tropoelastin and collagen type I were used as marker genes for fibroblasts, whereas surfactant protein (SP) A and SP-C were used as marker genes for distal epithelial cells. Mechanical strain, but not dexamethasone, significantly increased SP-C mRNA expression. Tropoelastin mRNA expression was upregulated by both mechanical strain and dexamethasone. No additive or synergistic effect was observed when cells were subjected to mechanical stretch in the presence of dexamethasone. Neither mechanical strain nor dexamethasone alone or in combination had any significant effect on the expression of SP-A mRNA. Dexamethasone decreased collagen type I mRNA expression, whereas mechanical strain had no effect. The increases in tropoelastin and SP-C mRNA levels induced by mechanical strain and/or dexamethasone were accompanied by increases in their heterogeneous nuclear RNA. In addition, the stretch- and glucocorticoid-induced alterations in tropoelastin and SP-C mRNA expression were abrogated with 10 µg/ml actinomycin D. These findings suggest that tropoelastin and SP-C genes are selectively stimulated by physical and/or hormonal factors at the transcriptional level in fetal lung fibroblasts and distal epithelial cells, respectively.
glucocorticoids; gene transcription; fetal lung cells
This article has been cited by other articles:
![]() |
R. D. Bland, R. Ertsey, L. M. Mokres, L. Xu, B. E. Jacobson, S. Jiang, C. M. Alvira, M. Rabinovitch, E. S. Shinwell, and A. Dixit Mechanical ventilation uncouples synthesis and assembly of elastin and increases apoptosis in lungs of newborn mice.: Prelude to defective alveolar septation during lung development? Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L3 - L14. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Starcher Mechanical ventilation and elastic fiber assembly Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L1 - L2. [Full Text] [PDF] |
||||
![]() |
A. D. Bird, K. H. Tan, P. F. Olsson, M. Zieba, S. J. Flecknoe, D. R. Liddicoat, R. Mollard, S. B. Hooper, and T. J. Cole Identification of glucocorticoid-regulated genes that control cell proliferation during murine respiratory development J. Physiol., November 15, 2007; 585(1): 187 - 201. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Mondrinos, S. Koutzaki, P. I. Lelkes, and C. M. Finck A tissue-engineered model of fetal distal lung tissue Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L639 - L650. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. D. Bland, L. Xu, R. Ertsey, M. Rabinovitch, K. H. Albertine, K. A. Wynn, V. H. Kumar, R. M. Ryan, D. D. Swartz, K. Csiszar, et al. Dysregulation of pulmonary elastin synthesis and assembly in preterm lambs with chronic lung disease Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1370 - L1384. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. Flecknoe, K. J. Crossley, G. M. Zuccala, J. E. Searle, B. J. Allison, M. J. Wallace, and S. B. Hooper Increased lung expansion alters lung growth but not alveolar epithelial cell differentiation in newborn lambs Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L454 - L461. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. F. Andrade, A. P. Wong, T. K. Waddell, S. Keshavjee, and M. Liu Cell-based tissue engineering for lung regeneration Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L510 - L518. [Abstract] [Full Text] [PDF] |
||||
![]() |
Mechanisms and Limits of Induced Postnatal Lung Growth Am. J. Respir. Crit. Care Med., August 1, 2004; 170(3): 319 - 343. [Full Text] [PDF] |
||||
![]() |
J. Sanchez-Esteban, Y. Wang, P. A. Gruppuso, and L. P. Rubin Mechanical Stretch Induces Fetal Type II Cell Differentiation Via an Epidermal Growth Factor Receptor-Extracellular-Regulated Protein Kinase Signaling Pathway Am. J. Respir. Cell Mol. Biol., January 1, 2004; 30(1): 76 - 83. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. Flecknoe, M. J. Wallace, M. L. Cock, R. Harding, and S. B. Hooper Changes in alveolar epithelial cell proportions during fetal and postnatal development in sheep Am J Physiol Lung Cell Mol Physiol, September 1, 2003; 285(3): L664 - L670. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Yoshizawa, C. J. Chapin, L. Sbragia, R. Ertsey, J. A. Gutierrez, C. T. Albanese, and J. A. Kitterman Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats Am J Physiol Lung Cell Mol Physiol, August 1, 2003; 285(2): L344 - L353. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. J. Joyce, M. J. Wallace, R. A. Pierce, R. Harding, and S. B. Hooper Sustained changes in lung expansion alter tropoelastin mRNA levels and elastin content in fetal sheep lungs Am J Physiol Lung Cell Mol Physiol, April 1, 2003; 284(4): L643 - L649. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. Foster, X. Yan, D. J. Bellotto, O. W. Moe, H. K. Hagler, A. S. Estrera, and C. C. W. Hsia Expression of epidermal growth factor and surfactant proteins during postnatal and compensatory lung growth Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L981 - L990. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Lodyga, X.-H. Bai, E. Mourgeon, B. Han, S. Keshavjee, and M. Liu Molecular cloning of actin filament-associated protein: a putative adaptor in stretch-induced Src activation Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L265 - L274. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Srinivasan, E. N. Bruce, P. K. Houtz, and M. C. Bruce Dexamethasone-induced changes in lung function are not prevented by concomitant treatment with retinoic acid Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L275 - L287. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Shafrir and G. Forgacs Mechanotransduction through the cytoskeleton Am J Physiol Cell Physiol, March 1, 2002; 282(3): C479 - C486. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Sanchez-Esteban, L. A. Cicchiello, Y. Wang, S.-W. Tsai, L. K. Williams, J. S. Torday, and L. P. Rubin Mechanical stretch promotes alveolar epithelial type II cell differentiation J Appl Physiol, August 1, 2001; 91(2): 589 - 595. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Liu and M. Post Cellular Responses to Mechanical Stress: Invited Review: Mechanochemical signal transduction in the fetal lung J Appl Physiol, November 1, 2000; 89(5): 2078 - 2084. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. T. Nakamura and P. B. McCray Jr. Fetal Airway Smooth-Muscle Contractility and Lung Development . A Player in the Band or Just Someone in the Audience? Am. J. Respir. Cell Mol. Biol., July 1, 2000; 23(1): 3 - 6. [Full Text] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |