Gene therapy for lung emphysema

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【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.