Hepatocyte Growth Factor Stimulates Proliferation of Respiratory Epithelial Cells during Postpneumonectomy Compensatory Lung Growth in Mice
- 1 May 2002
- journal article
- Published by American Thoracic Society in American Journal of Respiratory Cell and Molecular Biology
- Vol. 26 (5), 525-533
- https://doi.org/10.1165/ajrcmb.26.5.4714
Abstract
Although it is known that the lung undergoes compensatory growth after pulmonary resection, mechanisms by which lung cells exhibit compensatory proliferation are not well defined. We investigated the involvement of hepatocyte growth factor (HGF) in postpneumonectomy compensatory lung regeneration in mice, because HGF has mitogenic and morphogenic actions on lung epithelial cells. Following left pneumonectomy, alveolar and airway epithelial cells underwent compensatory DNA synthesis, reaching maximal levels 5 d after the surgery. Before changes in DNA synthesis in lung epithelial cells, expression of HGF mRNA and protein levels in the remaining lung, liver, and kidney were changed in response to left pneumonectomy, and these changes were associated with postoperative increases in plasma HGF levels. c-Met/HGF receptor expression was localized predominantly in alveolar type II and airway epithelial cells, whereas c-Met/HGF receptor mRNA expressions were transiently upregulated before the peak in lung DNA synthesis. Neutralization of endogenous HGF by an antibody in pneumonectomized mice suppressed the compensatory DNA synthesis in lung epithelial cells, whereas administration of recombinant HGF to pneumonectomized mice stimulated DNA synthesis in lung epithelial cells. These results strongly suggest that HGF has a role as a pulmotrophic factor in postpneumonectomy compensatory lung regeneration.Keywords
This publication has 36 references indexed in Scilit:
- Adrenergic Stimulation of Hepatocyte Growth Factor ExpressionBiochemical and Biophysical Research Communications, 1999
- Intratracheal instillation of keratinocyte growth factor decreases hyperoxia-induced mortality in rats.JCI Insight, 1995
- Compensatory lung growth occurs in adult dogs after right pneumonectomy.JCI Insight, 1994
- Keratinocyte growth factor and hepatocyte growth factor/scatter factor are heparin-binding growth factors for alveolar type II cells in fibroblast-conditioned medium.JCI Insight, 1993
- Up-regulation of hepatocyte growth factor gene expression by interleukin-1 in human skin fibroblastsBiochemical and Biophysical Research Communications, 1992
- Expressions of receptor gene for hepatocyte growth factor in kidney after unilateral nephrectomy and renal injuryBiochemical and Biophysical Research Communications, 1992
- Identification of the Hepatocyte Growth Factor Receptor As the c- met Proto-Oncogene ProductScience, 1991
- Biochemical Mechanisms of Cardiac HypertrophyAnnual Review of Physiology, 1987
- Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized ratsBiochemical and Biophysical Research Communications, 1984
- Morphogenetic and proliferative changes in the regenerating lung of the ratThe Anatomical Record, 1973