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Gene therapy for lung emphysema

肺气肿的基因治疗

基本信息

批准号：
18591557
负责人：
NAGAYASU Takeshi
金额：
$ 2.43万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591557/
关键词：
emphysema KGF regeneration 再生

项目摘要

【Objective】In the lung, the main targets of keratinocyte growth factor (KGF) are alveolar type 2 cells (ATII cells). KGF promotes survival and induces proliferation, migration, and differentiation of cells that express its receptor (KGF receptor; KGFR). Especially in some acute lung injuries, studies have demonstrated that KGF is involved in the regulation of both proliferation and differentiation of ATII cells. We hypothesized that the elevation of KGF levels may effect on lung regeneration in elastase induced lung emphysema.【Methods】Eight-week-old male BALB/c were used. Mice received a tracheal instillation of porcine pancreatic elastase. Following elastase injection, pKGF-FLAG was injected into each of the quadriceps muscle. Immediately electroporation was performed with pulse generator. KGF, KGFR expression, proliferative marker (PCNA), and in situ hybridization were performed in the emphysematous lung.【Results】The concentration of serum KGF was increased at day 4, and day 7 after transfection. The expression of KGF, KGFR, and PCNA in the lung were increased at day 4. Moreover KGF mRNA was highly detected in the emphysematous lung at day2-3. But we couldn't detect the improvement of emphysematous change by HE stain and arterial blood gas analysis.【Conclusion】 Our results indicate KGF gene therapy with electroporation has a therapeutic potential for elastase-induced lung emphysema.

[目的]在肺组织中，角质细胞生长因子（KGF）的主要作用靶点是肺泡2型细胞（ATII细胞）。KGF促进存活并诱导表达其受体（KGF受体; KGFR）的细胞的增殖、迁移和分化。特别是在一些急性肺损伤中，研究表明KGF参与调节ATII细胞的增殖和分化。我们推测KGF水平的升高可能影响弹性蛋白酶诱导的肺气肿的肺再生。[方法] 8周龄雄性BALB/c小鼠。小鼠接受猪胰弹性蛋白酶的气管滴注。在弹性蛋白酶注射后，将pKGF-FLAG注射到每个四头肌中。立即用脉冲发生器进行电穿孔。肺气肿肺组织中KGF、KGFR表达、增殖标记物（PCNA）和原位杂交。[结果]转染后第4天、第7天血清KGF浓度升高。KGF、KGFR和PCNA在肺中的表达在第4天增加。此外，KGF mRNA在第2 -3天的肺气肿肺中高度检测。但HE染色及动脉血气分析均未检测到肺气肿改变的改善。[结论]电穿孔KGF基因治疗对弹性蛋白酶诱导的肺气肿具有潜在的治疗作用。