Hepatocyte growth factor gene transfer to alveolar septa for effective suppression of lung fibrosis.
Hepatocyte growth factor gene transfer to alveolar septa for effective suppression of lung fibrosis.
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DOI：
10.1016/j.ymthe.2005.02.019
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发表时间：
2005-07
期刊：
影响因子：
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通讯作者：
Masaki Watanabe;M. Ebina;F. Orson;A. Nakamura;Kazuo Kubota;D. Koinuma;Kenichi Akiyama;M. Maemondo;S. Okouchi;M. Tahara;Kunio Matsumoto;Toshikazu Nakamura;T. Nukiwa
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文献类型：
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作者：
Masaki Watanabe;M. Ebina;F. Orson;A. Nakamura;Kazuo Kubota;D. Koinuma;Kenichi Akiyama;M. Maemondo;S. Okouchi;M. Tahara;Kunio Matsumoto;Toshikazu Nakamura;T. Nukiwa
我们研究了人肝细胞生长因子（hHGF）的治疗性基因转移到小鼠博莱霉素诱导的肺纤维化肺泡隔使用大聚集白蛋白-聚乙烯亚胺复合物（MAA-PEI）。C57 BL/6小鼠静脉注射MAA-PEI沿着1 μg pCAG.hHGF可增加肺泡毛细血管内皮细胞和上皮细胞对质粒的摄取，延长hHGF在肺中的表达，并诱导hHGF表达水平与单独注射10 μg hHGF表达质粒时相同。外源性hHGF基因表达增加了肺中内源性小鼠HGF，并显著降低了博来霉素损伤后TNF-α、IL-6和胶原合成。由于HGF减少博来霉素损伤后GFP标记的骨髓源性干细胞的数量，因此HGF的主要机制可能是防止细胞凋亡，正如体外实验所表明的那样。这种新的HGF基因转移的方法，肺泡隔与非刺激性MAA-PEI共轭物可能有前途的临床应用。
We examined therapeutic gene transfer of human hepatocyte growth factor (hHGF) to alveolar septa in mouse bleomycin-induced lung fibrosis using macroaggregated albumin-polyethylenimine complex (MAA-PEI). Intravenous administration of MAA-PEI along with 1 μg pCAG.hHGF to C57BL/6 mice increased the uptake of plasmids into alveolar capillary endothelial cells and epithelial cells, prolonged hHGF expression in the lung, and induced a level of hHGF expression equal to that seen with 10 μg of hHGF-expression plasmids alone. The exogenous source of hHGF gene expression increased the endogenous mouse HGF in the lungs and significantly decreased TNF-α, IL-6, and collagen synthesis after bleomycin injury. Because GFP-labeled bone marrow-derived stem cells after bleomycin injury were reduced in number by HGF, the primary mechanism of HGF is likely to be the prevention of apoptosis, as has been suggested byin vitroexperiments. This novel HGF gene transfer method to alveolar septa with nonstimulatory MAA-PEI conjugates may have promising clinical applications.