Simultaneous or delayed administration of hepatocyte growth factor equally represses the fibrotic changes in murine lung injury induced by bleomycin. A morphologic study.
Hepatocyte growth factor (HGF) is a humoral mediator of epithelial-mesenchymal interactions, acting on a variety of epithelial cells as mitogen, motogen, and morphogen. Exogenous HGF acts as a hepatotrophic factor and a renotrophic factor during experimental injury. To investigate whether HGF has a pulmotrophic function, human recombinant HGF was administered to C57BL/6 mice with severe lung injury by bleomycin (BLM). Low dose simultaneous and continuous administration of HGF (50 micrograms/mouse/7 d) with BLM (100 mg/mouse/7 d) repressed fibrotic morphological changes at 2 and 4 wk. Ashcroft score showed a significant difference in lung fibrosis with and without HGF at 4 wk (3.7 +/- 0.4 versus 4.9 +/- 0.3, p < 0.05). Furthermore, either simultaneous or delayed administration of high dose HGF (280 micrograms/mouse/14 d) equally repressed fibrotic changes by BLM when examined at 4 wk (Ashcroft score: 2.6 +/- 0.4 and 2.4 +/- 0.2 versus 4.1 +/- 0.2, p < 0.01). Hydroxyproline content in the lungs was significantly lower in mice with either simultaneous or delayed administration of high dose HGF as compared to those administered BLM alone (121.8 +/- 8.1% and 113.2 +/- 6.2% versus 162.7 +/- 4.6%, p < 0.001). These findings indicate that exogenous HGF acts as a pulmotrophic factor in vivo and prevents the progression of BLM-induced lung injury when administered in either a simultaneous or delayed fashion. HGF may be a potent candidate to prevent or treat lung fibrosis.
Yaekashiwa
M
M
Department of Respiratory Oncology and Molecular Medicine, Tohoku University, Sendai, Japan. yaesan@idac.tohoku.ac.jp
Nakayama
S
S
Ohnuma
K
K
Sakai
T
T
Abe
T
T
Satoh
K
K
Matsumoto
K
K
Nakamura
T
T
Takahashi
T
T
Nukiwa
T
T
D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage* / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000008:administration & dosage; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000473:pathology*
D011994:Recombinant Proteins; D001761:Bleomycin; D017228:Hepatocyte Growth Factor