| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 BY ALVEOLAR EPITHELIAL CELLS RESULTS IN PULMONARY FIBROSIS
1 Department of Medicine, University of British Columbia, Vanocuver, BC, Canada
2 Department of Surgery, Vancouver Hospital, Vancouver, BC, Canada
3 Department of Pathology, BC Cancer Agency, Vancouver, BC, Canada
4 School of Medicine, University of Miami, Miami, FL, USA
* To whom correspondence should be addressed. E-mail: nkhalil{at}interchange.ubc.ca.
Idiopathic pulmonary fibrosis (IPF) is a progressive fatal fibrotic lung disease. Transforming growth factor-beta 1 (TGF-
1) is present in a biologically active conformation in the epithelial cells lining lesions with advanced IPF. To determine the role of aberrant expression of biologically active TGF-1 by alveolar epithelial cells (AECs), the AECs of explanted normal rat lungs were transfected with the TGF-1 gene using the retrovirus pMX-L-s223, 225-TGF-1. In situ hybridization using a digoxigenin labeled cDNA of the puromycin resistance gene contained in the pMX demonstrated that pMX-L-s233, 225-TGF-1 was selectively transfected into AECs of the explants. Conditioned media (CM) overlying explants obtained 7 days after being treated with pMX-L-s223, 225-TGF-1 contained 14.5±3.15 pg/ml of active TGF-1. Using Mason's Trichrome staining of explant sections obtained 14 days after transfection there were lesions similar to those in IPF, characterized by type II AEC hyperplasia, interstitial thickening, extensive increase in interstitial and subepithelial collagen, an increase in the number of fibroblasts, and areas resembling fibroblast buds. Collagens I, III, IV, V and fibronectin were increased in explants treated with pMX-L-s223, 225-TGF-1. The findings in the current study suggest that IPF may be a disorder of epithelial cells and not inflammatory cells.
This article has been cited by other articles:
|
|
 |
|
  J. Xu, E. T. Gonzalez, S. S. Iyer, V. Mac, A. L. Mora, R. L. Sutliff, A. Reed, K. L. Brigham, P. Kelly, and M. Rojas Use of Senescence-Accelerated Mouse Model in Bleomycin-Induced Lung Injury Suggests That Bone Marrow-Derived Cells Can Alter the Outcome of Lung Injury in Aged Mice J Gerontol A Biol Sci Med Sci, July 1, 2009; 64A(7): 731 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Myllarniemi, P. Lindholm, M. J. Ryynanen, C. R. Kliment, K. Salmenkivi, J. Keski-Oja, V. L. Kinnula, T. D. Oury, and K. Koli Gremlin-mediated Decrease in Bone Morphogenetic Protein Signaling Promotes Pulmonary Fibrosis Am. J. Respir. Crit. Care Med., February 1, 2008; 177(3): 321 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Alcorn, L. M. Rinaldi, E. F. Jaffe, M. van Loon, J. H. T. Bates, Y. M. W. Janssen-Heininger, and C. G. Irvin Transforming Growth Factor-beta1 Suppresses Airway Hyperresponsiveness in Allergic Airway Disease Am. J. Respir. Crit. Care Med., November 15, 2007; 176(10): 974 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. Willis and Z. Borok TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L525 - L534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Myerburg, J. D. Latoche, E. E. McKenna, L. P. Stabile, J. S. Siegfried, C. A. Feghali-Bostwick, and J. M. Pilewski Hepatocyte growth factor and other fibroblast secretions modulate the phenotype of human bronchial epithelial cells Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1352 - L1360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-R. Kang, C. G. Lee, R. J. Homer, and J. A. Elias Semaphorin 7A plays a critical role in TGF-{beta}1-induced pulmonary fibrosis J. Exp. Med., May 14, 2007; 204(5): 1083 - 1093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Khalil, A. Churg, N. Muller, and R. O'Connor Environmental, Inhaled and Ingested Causes of Pulmonary Fibrosis Toxicol Pathol, January 1, 2007; 35(1): 86 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Li, S. Oparil, L. Novak, X. Cao, W. Shi, J. Lucas, and Y.-F. Chen ANP signaling inhibits TGF-beta-induced Smad2 and Smad3 nuclear translocation and extracellular matrix expression in rat pulmonary arterial smooth muscle cells J Appl Physiol, January 1, 2007; 102(1): 390 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu, A. L. Mora, J. LaVoy, K. L. Brigham, and M. Rojas Increased bleomycin-induced lung injury in mice deficient in the transcription factor T-bet Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L658 - L667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Karagiannidis, V. Velehorschi, B. Obertrifter, H.-N. Macha, A. Linder, and L. Freitag High-Level Expression of Matrix-Associated Transforming Growth Factor-{beta}1 in Benign Airway Stenosis Chest, May 1, 2006; 129(5): 1298 - 1304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-F. Chen, J.-A. Feng, P. Li, D. Xing, Y. Zhang, R. Serra, N. Ambalavanan, E. Majid-Hassan, and S. Oparil Dominant negative mutation of the TGF-beta receptor blocks hypoxia-induced pulmonary vascular remodeling J Appl Physiol, February 1, 2006; 100(2): 564 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Mora, C. R. Woods, A. Garcia, J. Xu, M. Rojas, S. H. Speck, J. Roman, K. L. Brigham, and A. A. Stecenko Lung infection with {gamma}-herpesvirus induces progressive pulmonary fibrosis in Th2-biased mice Am J Physiol Lung Cell Mol Physiol, November 1, 2005; 289(5): L711 - L721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Kelly, R. Leigh, P. Bonniaud, R. Ellis, J. Wattie, M. J. Smith, G. Martin, M. Panju, M. D. Inman, and J. Gauldie Epithelial Expression of Profibrotic Mediators in a Model of Allergen-Induced Airway Remodeling Am. J. Respir. Cell Mol. Biol., February 1, 2005; 32(2): 99 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kida, M. Yoshida, S. Hoshino, K. Inoue, Y. Yano, M. Yanagita, T. Kumagai, T. Osaki, I. Tachibana, Y. Saeki, et al. Protective effect of IL-6 on alveolar epithelial cell death induced by hydrogen peroxide Am J Physiol Lung Cell Mol Physiol, February 1, 2005; 288(2): L342 - L349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Kunz, M. R. Jadus, G. D. Kukes, F. Kramer, V. N. Nguyen, and S. A. Sasse Intrapleural Injection of Transforming Growth Factor-{beta} Antibody Inhibits Pleural Fibrosis in Empyema Chest, November 1, 2004; 126(5): 1636 - 1644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Olman and M. A. Matthay Transforming growth factor-{beta} induces fibrosis in immune cell-depleted lungs Am J Physiol Lung Cell Mol Physiol, September 1, 2003; 285(3): L522 - L526. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
