Hepatocyte growth factor attenuates collagen accumulation in a murine model of pulmonary fibrosis
Hepatocyte growth factor attenuates collagen accumulation in a murine model of pulmonary fibrosis
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DOI：
10.1164/ajrccm.162.6.9908097
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发表时间：
2000-12-01
影响因子：
24.7
通讯作者：
Marshall, BC
中科院分区：
文献类型：
--
作者：
Dohi, M;Hasegawa, T;Marshall, BC
我们研究了重组人肝细胞生长因子（HGF）对正常小鼠肺上皮细胞增殖和博莱霉素诱导的肺损伤后修复过程的体内影响。C57 BL/6小鼠气管内注射100 μ g rhHGF可导致支气管和肺泡上皮细胞增殖，如增殖细胞核抗原（PCNA）染色的细胞数量增加所示。在肺内注射博来霉素后第3天和第6天，通过给予100 μ g rhHGF检测HGF对肺修复过程的影响。我们发现，肝细胞生长因子显着衰减博莱霉素诱导的胶原蛋白的积累所确定的羟脯氨酸含量的定量和评分的纤维化程度。为了探索HGF的有益作用的潜在机制，我们用A549肺上皮细胞进行了体外研究，发现HGF增强了细胞表面纤溶酶的产生、u-PA活性的表达和细胞迁移。综上所述，肝细胞生长因子在体内外均对上皮细胞有较强的作用，提示其可能在肺纤维化的治疗中发挥作用。
We investigated the in vivo effects of recombinant human hepatocyte growth factor (HGF) on epithelial cell proliferation in normal mouse lung and on the repair process that follows bleomycin-induced lung injury. Intratracheal administration of 100 mug of rhHGF to C57BL/6 mice led to proliferation of bronchial and alveolar epithelial cells as indicated by an increased number of cells staining for proliferating cell nuclear antigen (PCNA). The effect of HGF on the lung repair process was examined by administration of 100 mug of rhHGF on Day 3 and Day 6 after intratracheal injection of bleomycin to mice. We found that HGF significantly attenuated collagen accumulation induced by bleomycin as determined by quantitation of hydroxyproline content and by scoring of the extent of fibrosis. To explore the potential mechanisms involved in the beneficial effects of HGF, we performed in vitro studies with A549 pulmonary epithelial cells and found that HGF enhanced cell surface plasmin generation, expression of u-PA activity, and cell migration. In summary, HGF has potent in vivo and in vitro effects an epithelial cells, which suggests it may have a role in the therapy of pulmonary fibrosis.