Simultaneous or delayed administration of hepatocyte growth factor equally represses the fibrotic changes in murine lung injury induced by bleomycin - A morphologic study
Simultaneous or delayed administration of hepatocyte growth factor equally represses the fibrotic changes in murine lung injury induced by bleomycin - A morphologic study
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DOI：
10.1164/ajrccm.156.6.9611057
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发表时间：
1997-12-01
影响因子：
24.7
通讯作者：
Nukiwa, T
中科院分区：
文献类型：
--
作者：
Yaekashiwa, M;Nakayama, S;Nukiwa, T
肝细胞生长因子（HGF）是上皮细胞-间质细胞相互作用的体液介质，作为促分裂原、促运动原和促形态发生剂作用于多种上皮细胞。外源性肝细胞生长因子在实验性损伤中作为肝营养因子和肾营养因子发挥作用。为了研究肝细胞生长因子是否具有肺营养功能，将人重组肝细胞生长因子给予博莱霉素（BLM）造成严重肺损伤的C57 BL/6小鼠。低剂量HGF（50 μ g/mouse/7 d）与BLM（100 mg/mouse/7 d）同时和连续给药抑制了2和4周时的纤维化形态学变化。Ashcroft评分显示在4周时有和没有HGF的肺纤维化的显著差异（3.7 +/- 0.4对4.9 +/- 0.3，p < 0.05）。此外，在第4周检查时，同时或延迟给予高剂量HGF（280 μ g/小鼠/14天）同样抑制了BLM引起的纤维化变化（Ashcroft评分：2.6 +/- 0.4和2.4 +/-0.2对4.1 +/- 0.2，p < 0.01）。与单独给予BLM的小鼠相比，同时或延迟给予高剂量HGF的小鼠肺中羟脯氨酸含量显著降低（121.8 +/- 8.1%和113.2 +/- 6.2%对162.7 +/-4.6%，p < 0.001）。这些结果表明，外源性肝细胞生长因子作为一种肺营养因子在体内，并防止BLM诱导的肺损伤的进展时，无论是在同时或延迟的方式管理。HGF可能是预防或治疗肺纤维化的有效候选物。
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.