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首页> 外文期刊>Acta histochemica et cytochemica. >Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice
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Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice

机译：角质形成细胞生长因子基因电穿孔进入骨骼肌作为一种新的基因治疗弹性蛋白酶诱导的肺气肿的小鼠治疗方法

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Pulmonary emphysema is a progressive disease with airspace destruction and an effective therapy is needed. Keratinocyte growth factor (KGF) promotes pulmonary epithelial proliferation and has the potential to induce lung regeneration. The aim of this study was to determine the possibility of using KGF gene therapy for treatment of a mouse emphysema model induced by porcine pancreatic elastase (PPE). Eight-week-old BALB/c male mice treated with intra-tracheal PPE administration were transfected with 80 μg of a recombinant human KGF (rhKGF)-expressing FLAG-CMV14 plasmid (pKGF-FLAG gene), or with the pFLAG gene expressing plasmid as a control, into the quadriceps muscle by electroporation. In the lung, the expression of proliferating cell nuclear antigen (PCNA) was augmented, and surfactant protein A (SP-A) and KGF receptor (KGFR) were co-expressed in PCNA-positive cells. Moreover, endogenous KGF and KGFR gene expression increased significantly by pKGF-FLAG gene transfection. Arterial blood gas analysis revealed that the PaO2 level was not significantly reduced on day 14 after PPE instillation with pKGF-FLAG gene transfection compared to that of normal mice. These results indicated that KGF gene therapy with electroporation stimulated lung epithelial proliferation and protected depression of pulmonary function in a mouse emphysema model, suggesting a possible method of treating pulmonary emphysema.
机译：肺气肿是一种进展性疾病，伴有空域破坏，需要有效的治疗方法。角质形成细胞生长因子（KGF）促进肺上皮细胞增殖，并具有诱导肺再生的潜力。这项研究的目的是确定使用KGF基因疗法治疗由猪胰弹性蛋白酶（PPE）诱发的小鼠肺气肿模型的可能性。将经气管内PPE处理的八周大的BALB / c雄性小鼠用80μg表达重组人KGF（rhKGF）的FLAG-CMV14质粒（pKGF-FLAG基因）或pFLAG基因表达质粒转染作为对照，通过电穿孔进入股四头肌。在肺中，增殖细胞核抗原（PCNA）的表达增加，并且在PCNA阳性细胞中共表达表面活性剂蛋白A（SP-A）和KGF受体（KGFR）。而且，通过pKGF-FLAG基因转染，内源性KGF和KGFR基因表达显着增加。动脉血气分析表明，与正常小鼠相比，用pKGF-FLAG基因转染PPE后第14天，PaO 2 水平没有显着降低。这些结果表明，在小鼠肺气肿模型中，电穿孔的KGF基因疗法可刺激肺上皮细胞增殖，并保护肺功能的降低，提示了治疗肺气肿的一种可能方法。

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