Intranasal HGF administration ameliorates the physiologic and morphologic changes in lung emphysema
Intranasal HGF administration ameliorates the physiologic and morphologic changes in lung emphysema
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DOI：
10.1038/mt.2008.137
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发表时间：
2008-08-01
影响因子：
12.4
通讯作者：
Nakamura, Toshikazu
中科院分区：
文献类型：
--
作者：
Hegab, Ahmed E.;Kubo, Hiroshi;Nakamura, Toshikazu
肝细胞生长因子（HGF）对干细胞、上皮细胞增殖和伤口愈合具有多种生物学作用。在这项研究中，我们研究了鼻内HGF对弹性蛋白酶诱导的肺气肿的可能治疗益处，并评估了干/祖细胞在此过程中的作用。在小鼠肺气肿建立后，每周两次给予HGF，持续1-4周。吸入HGF可明显改善肺泡腔扩大和肺泡壁破坏。此外，升高的静态肺顺应性在HGF治疗2周内恢复至对照水平。HGF对干细胞标志物c-kit、干细胞抗原1（Sca-1）和CD 34的表达也有显著影响。大多数c-kit（+）细胞是骨髓来源的，而大多数Sca-1（+）是肺内源性细胞。CD 34（+）细胞来自两种来源，一部分内源性CD 34（+）细胞也是Sca-1（+）。此外，HGF增加增殖细胞核抗原（PCNA）和细胞角蛋白-19的表达水平。此外，他们的免疫组化染色模式共定位，上皮增殖的指示。研究结果表明，HGF鼻内治疗逆转肺气肿的生理和形态学变化，可能是通过干细胞动员和肺泡再生，提供了一种非手术治疗，并表明在人类中实现类似效果的可能性。
Hepatocyte growth factor (HGF) has multiple biological effects on stem cells, epithelial proliferation, and wound healing. In this study, we investigated a possible therapeutic benefit of intranasal HGF on elastase-induced emphysema, and assessed the role of stem/progenitor cells in this process. HGF was given twice a week for 1-4 weeks after the establishment of emphysema in mice. HGF inhalation significantly ameliorated the enlargement of airspaces and alveolar wall destruction. Also, elevated static lung compliance returned to control levels within 2 weeks of HGF treatment. The expressions of stem-cell markers, c-kit, stem-cell antigen 1 (Sca-1), and CD34 were also significantly influenced by HGF. Most of the c-kit(+) cells were bone marrow derived, while most Sca-1(+) were lung endogenous cells. CD34(+) cells were from both sources, and a portion of the endogenous CD34(+) cells was also Sca-1(+). Further, HGF increased the expression levels of proliferating cell nuclear antigen (PCNA) and cytokeratin-19. Also, their immunohistochemical staining patterns were colocalized, indicative of epithelial multiplication. The results of the study show that intranasal treatment with HGF reverses both the physiological and morphometric changes of lung emphysema, possibly through stemcell mobilization and alveolar regeneration, providing a nonsurgical treatment and suggesting the possibility of achieving a similar effect in humans.