| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada
Keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are known mitogens for normal alveolar Type 2 cells in vitro and in vivo. We wished to determine whether these two growth factors are involved in lung repair after epithelial cell necrosis by determining the levels of each factor in lung lavage fluid collected serially after bleomycin-induced injury, and how these values relate specifically to proliferation of bronchiolar and alveolar epithelial cells. Rats received an intratracheal injection of 1 unit bleomycin in 0.5 ml water and were killed at intervals up to 4 weeks with 1 µCi/g tritiated thymidine injected 1 hour before death. Early necrosis of bronchiolar epithelial (BR) cells and Type 1 alveolar epithelium was followed by an increase in inflammatory cell numbers and high protein levels in bronchoalveolar lavage (BAL) fluids. In addition, the levels of KGF and HGF, measured by enzyme-linked immunosorbent assay in BAL, increased as early as 3 days and peaked at 7–14 days, when KGF was measured at 160 pg/ml (n = 50) and HGF reached 460 pg/ml (n = 40). Both values dropped sharply after 2 weeks. Epithelial cell proliferation was quantitated as percentage of labeled cells in autoradiographs of methacrylate sections. Labeling of BR cells predominated in the first week and peaked at 7% at 3 days. Type 2 cell proliferation was delayed somewhat but occurred in 3 to 10 days with a peak of 7% labeled cells at 1 week. The results demonstrate that both HGF and KGF are present in the lung in greatly increased amounts soon after bleomycin-induced epithelial cell necrosis. These high levels are associated with both BR and alveolar epithelial cell proliferation.
This article has been cited by other articles:
 |
|
 |
|
  C. Quesnel, S. Marchand-Adam, A. Fabre, J. Marchal-Somme, I. Philip, S. Lasocki, V. Lecon, B. Crestani, and M. Dehoux Regulation of hepatocyte growth factor secretion by fibroblasts in patients with acute lung injury Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L334 - L343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gazdhar, P. Fachinger, C. van Leer, J. Pierog, M. Gugger, R. Friis, R. A. Schmid, and T. Geiser Gene transfer of hepatocyte growth factor by electroporation reduces bleomycin-induced lung fibrosis Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L529 - L536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Matsuoka, T. H. Sisson, T. Nishiuma, and R. H. Simon Plasminogen-Mediated Activation and Release of Hepatocyte Growth Factor from Extracellular Matrix Am. J. Respir. Cell Mol. Biol., December 1, 2006; 35(6): 705 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W. Finch and J. S. Rubin Keratinocyte growth factor expression and activity in cancer: implications for use in patients with solid tumors. J Natl Cancer Inst, June 21, 2006; 98(12): 812 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cepkova and M. A. Matthay Pharmacotherapy of acute lung injury and the acute respiratory distress syndrome. J Intensive Care Med, May 1, 2006; 21(3): 119 - 143. [Abstract] [PDF]
|
|
|
|
 |
|
 O. Alpdogan, V. M. Hubbard, O. M. Smith, N. Patel, S. Lu, G. L. Goldberg, D. H. Gray, J. Feinman, A. A. Kochman, J. M. Eng, et al. Keratinocyte growth factor (KGF) is required for postnatal thymic regeneration Blood, March 15, 2006; 107(6): 2453 - 2460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Padela, J. Cabacungan, S. Shek, R. Belcastro, M. Yi, R. P. Jankov, and A. K. Tanswell Hepatocyte Growth Factor Is Required for Alveologenesis in the Neonatal Rat Am. J. Respir. Crit. Care Med., October 1, 2005; 172(7): 907 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Plantier, S. Marchand-Adam, J. Marchal-Somme, G. Leseche, M. Fournier, M. Dehoux, M. Aubier, and B. Crestani Defect of hepatocyte growth factor production by fibroblasts in human pulmonary emphysema Am J Physiol Lung Cell Mol Physiol, April 1, 2005; 288(4): L641 - L647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Day, G. Thiel, J. Lum, R. D. Chevere, Y. Yang, J. Stevens, L. Sibert, and B. L. Fanburg Hepatocyte Growth Factor Regulates Angiotensin Converting Enzyme Expression J. Biol. Chem., March 5, 2004; 279(10): 8792 - 8801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Hattori, S. Mizuno, Y. Yoshida, K. Chin, M. Mishima, T. H. Sisson, R. H. Simon, T. Nakamura, and M. Miyake The Plasminogen Activation System Reduces Fibrosis in the Lung by a Hepatocyte Growth Factor-Dependent Mechanism Am. J. Pathol., March 1, 2004; 164(3): 1091 - 1098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wislez, N. Rabbe, J. Marchal, B. Milleron, B. Crestani, C. Mayaud, M. Antoine, P. Soler, and J. Cadranel Hepatocyte Growth Factor Production by Neutrophils Infiltrating Bronchioloalveolar Subtype Pulmonary Adenocarcinoma: Role in Tumor Progression and Death Cancer Res., March 15, 2003; 63(6): 1405 - 1412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Maniscalco, R. H. Watkins, M. A. O'Reilly, and C. P. Shea Increased epithelial cell proliferation in very premature baboons with chronic lung disease Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L991 - L1001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lassus, I. Nupponen, A. Kari, M. Pohjavuori, and S. Andersson Early Postnatal Dexamethasone Decreases Hepatocyte Growth Factor in Tracheal Aspirate Fluid From Premature Infants Pediatrics, October 1, 2002; 110(4): 768 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Mason Hepatocyte Growth Factor . The Key to Alveolar Septation? Am. J. Respir. Cell Mol. Biol., May 1, 2002; 26(5): 517 - 520. [Full Text] [PDF]
|
|
|
|
|
|
L. B. Ware and M. A. Matthay Keratinocyte and hepatocyte growth factors in the lung: roles in lung development, inflammation, and repair Am J Physiol Lung Cell Mol Physiol, May 1, 2002; 282(5): L924 - L940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. T. HASTIE, W. K. KRAFT, K. B. NYCE, J. G. ZANGRILLI, A. I. MUSANI, J. E. FISH, and S. P. PETERS Asthmatic Epithelial Cell Proliferation and Stimulation of Collagen Production . Human Asthmatic Epithelial Cells Stimulate Collagen Type III Production by Human Lung Myofibroblasts after Segmental Allergen Challenge Am. J. Respir. Crit. Care Med., January 15, 2002; 165(2): 266 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Day, Y. Yang, Y. J. Suzuki, J. Stevens, R. Pathi, A. Perlmutter, B. L. Fanburg, and J. J. Lanzillo Bleomycin Upregulates Gene Expression of Angiotensin-Converting Enzyme via Mitogen-Activated Protein Kinase and Early Growth Response 1 Transcription Factor Am. J. Respir. Cell Mol. Biol., November 1, 2001; 25(5): 613 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Welsh, B. P. H. Guery, B. P. Deboisblanc, E. P. Dobard, C. Creusy, D. Mercante, S. Nelson, W. R. Summer, and C. M. Mason Keratinocyte growth factor attenuates hydrostatic pulmonary edema in an isolated, perfused rat lung model Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1311 - H1317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Awasthi and R. J. King PKC, p42/p44 MAPK, and p38 MAPK are required for HGF-induced proliferation of H441 cells Am J Physiol Lung Cell Mol Physiol, November 1, 2000; 279(5): L942 - L949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Y. R. Adamson, J. Bakowska, and H. Prieditis Proliferation of Rat Pleural Mesothelial Cells in Response to Hepatocyte and Keratinocyte Growth Factors Am. J. Respir. Cell Mol. Biol., September 1, 2000; 23(3): 345 - 349. [Abstract] [Full Text]
|
|
|
|
|
|
T. Pan, L. D. Nielsen, M. J. Allen, K. M. Shannon, J. M. Shannon, M. Selman, and Robert. J. Mason Serum SP-D is a marker of lung injury in rats Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L824 - L832. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
