Simultaneous or delayed administration of hepatocyte growth factor equally represses the fibrotic changes in murine lung injury induced by bleomycin - A morphologic study

被引:183
作者
Yaekashiwa, M
Nakayama, S
Ohnuma, K
Sakai, T
Abe, T
Satoh, K
Matsumoto, K
Nakamura, T
Takahashi, T
Nukiwa, T
机构
[1] TOHOKU UNIV,INST DEV AGING & CANC,DEPT PATHOL,DIV ORGAN PATHOPHYSIOL,SENDAI,MIYAGI 98077,JAPAN
[2] OSAKA UNIV,SCH MED,BIOMED RES CTR,DEPT ONCOL,DIV BIOCHEM,OSAKA 553,JAPAN
关键词
D O I
10.1164/ajrccm.156.6.9611057
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 mu g/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 mu g/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.
引用
收藏
页码:1937 / 1944
页数:8
相关论文
共 54 条
[1]   SIMPLE METHOD OF ESTIMATING SEVERITY OF PULMONARY FIBROSIS ON A NUMERICAL SCALE [J].
ASHCROFT, T ;
SIMPSON, JM ;
TIMBRELL, V .
JOURNAL OF CLINICAL PATHOLOGY, 1988, 41 (04) :467-470
[2]   INCREASED OXIDATION OF EXTRACELLULAR GLUTATHIONE BY BRONCHOALVEOLAR INFLAMMATORY CELLS IN DIFFUSE FIBROSING ALVEOLITIS [J].
BEHR, J ;
DEGENKOLB, B ;
MAIER, K ;
BRAUN, B ;
BEINERT, T ;
KROMBACH, F ;
VOGELMEIER, C ;
FRUHMANN, G .
EUROPEAN RESPIRATORY JOURNAL, 1995, 8 (08) :1286-1292
[3]  
BORDER WA, 1994, NEW ENGL J MED, V331, P1286
[4]   IDENTIFICATION OF THE HEPATOCYTE GROWTH-FACTOR RECEPTOR AS THE C-MET PROTOONCOGENE PRODUCT [J].
BOTTARO, DP ;
RUBIN, JS ;
FALETTO, DL ;
CHAN, AML ;
KMIECIK, TE ;
VANDEWOUDE, GF ;
AARONSON, SA .
SCIENCE, 1991, 251 (4995) :802-804
[5]   TRANSFORMING GROWTH FACTOR-BETA-1 IS PRESENT AT SITES OF EXTRACELLULAR-MATRIX GENE-EXPRESSION IN HUMAN PULMONARY FIBROSIS [J].
BROEKELMANN, TJ ;
LIMPER, AH ;
COLBY, TV ;
MCDONALD, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (15) :6642-6646
[6]  
BROS P, 1995, LANCET, V345, P293
[7]   ALVEOLITIS AND COLLAPSE IN THE PATHOGENESIS OF PULMONARY FIBROSIS [J].
BURKHARDT, A .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1989, 140 (02) :513-524
[8]   PURIFICATION AND PARTIAL CHARACTERIZATION OF HEPATOCYTE GROWTH-FACTOR FROM PLASMA OF A PATIENT WITH FULMINANT HEPATIC-FAILURE [J].
GOHDA, E ;
TSUBOUCHI, H ;
NAKAYAMA, H ;
HIRONO, S ;
SAKIYAMA, O ;
TAKAHASHI, K ;
MIYAZAKI, H ;
HASHIMOTO, S ;
DAIKUHARA, Y .
JOURNAL OF CLINICAL INVESTIGATION, 1988, 81 (02) :414-419
[9]   DETERMINATION OF HYDROXYPROLINE BY HIGH-PRESSURE LIQUID-CHROMATOGRAPHY [J].
GREEN, GD ;
REAGAN, K .
ANALYTICAL BIOCHEMISTRY, 1992, 201 (02) :265-269
[10]  
HARRISON JH, 1987, J PHARMACOL EXP THER, V243, P1185