Ishizawa Kota, Kubo Hiroshi, Yamada Mitsuhiro, Kobayashi Seiichi, Suzuki Takashi, Mizuno Shinya, Nakamura Toshikazu, Sasaki Hidetada
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Miyagi 980-8574, Japan.
Biochem Biophys Res Commun. 2004 Nov 5;324(1):276-80. doi: 10.1016/j.bbrc.2004.09.049.
Circulating endothelial progenitor cells (EPCs) play a pivotal role in angiogenesis. Hepatocyte growth factor (HGF) is known to induce proliferation and motility in endothelial cells, and to play a role in mitogenic and morphogenic actions. However, the role of HGF in EPC mobilization has not been clearly described yet. We investigated the effect of HGF on mobilizing EPCs and on angiogenesis in elastase-induced lung injury. HGF significantly increased the triple-positive (Sca-1(+), Flk-1(+), and c-kit(+)) fraction in peripheral mononuclear cells in mice. The bone marrow-derived cells were recruited into the injured lungs, where they differentiated to capillary endothelial cells. HGF induced proliferation of both bone marrow-derived and resident endothelial cells in the alveolar wall. In conclusion, the present study suggests that HGF induces EPC mobilization from the bone marrow and enhances the proliferation of endothelial cells in vivo. These complex effects induced by HGF orchestrate pulmonary regeneration in emphysematous lung parenchyma.
循环内皮祖细胞（EPCs）在血管生成中起关键作用。已知肝细胞生长因子（HGF）可诱导内皮细胞增殖和迁移，并在促有丝分裂和形态发生作用中发挥作用。然而，HGF在EPC动员中的作用尚未得到明确描述。我们研究了HGF对弹性蛋白酶诱导的肺损伤中EPC动员和血管生成的影响。HGF显著增加了小鼠外周血单个核细胞中三阳性（Sca-1(+)、Flk-1(+)和c-kit(+)）细胞比例。骨髓来源的细胞被募集到受损肺组织中，并在那里分化为毛细血管内皮细胞。HGF诱导肺泡壁中骨髓来源的内皮细胞和驻留内皮细胞增殖。总之，本研究表明HGF诱导骨髓中EPC动员，并增强体内内皮细胞增殖。HGF诱导的这些复杂效应协调了肺气肿肺实质中的肺再生。
