Gene therapy for lung emphysema

[目的]在肺组织中，角质形成细胞生长因子(KGF)的主要靶点是肺泡2型细胞(ATII细胞)。KGF促进表达其受体(KGF受体；KGFR)的细胞的存活、增殖、迁移和分化。特别是在一些急性肺损伤中，研究表明KGF参与了ATII细胞的增殖和分化的调节。我们推测在弹性酶诱导的肺气肿模型中，KGF水平的升高可能影响肺再生。小鼠接受了猪胰腺弹性酶的气管滴注。注射弹性酶后，股四头肌内注射pKGF-FLAG。立即用脉冲发生器进行电穿孔。对肺气肿大鼠肺组织进行KGF、KGFR表达、增殖标记物(增殖细胞核抗原)和原位杂交检测。肺组织中KGF、KGFR和增殖细胞核抗原的表达在第4天开始增加，且在第2~3天肺气肿肺组织中有较高的表达。[结论]KGF基因电穿孔治疗对弹性酶诱导的肺气肿有一定的治疗潜力。

【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.