Keratinocyte growth factor is a potent modulator of lung compensatory regeneration after lobectomy

目的：肺切除后肺代偿性生长。然而，肺组织再生的分子机制仍不清楚。角质形成细胞生长因子(KGF)在肺组织中表达，被认为是肺上皮细胞可能的有丝分裂原。本研究的目的是明确KGF及其受体(KGFR)在三叶切除后大鼠肺再生中的作用以及外源性KGF表达基因的影响。手术组行右三叶切除，假手术组行开胸手术。手术组将KGF-FLAG或FLAG表达载体通过电穿孔直接转入肺内。术后14天检测右肺组织中KGF、KGFR的表达，并用增殖细胞核抗原检测肺泡细胞增殖指数。结果：三叶切除后第4天，肺上皮细胞中增殖细胞核抗原、KGF和KGFR的表达均显著增加。在三叶切除后第4天，KGF-FLAG表达载体的表达进一步显著增强，而FLAG表达载体的表达并未改变其表达的增强。结论：外源性KGF可诱导肺泡上皮细胞增殖，促进代偿性再生；电穿孔可显著促进肺上皮细胞增殖。

Objective : Pulmonary resection is followed by lung compensatory growth. However, the molecular mechanism underlying lung tissue regeneration remains unclear. Keratinocyte growth factor (KGF) is expressed in lung tissue and is considered a possible mitogen for lung epithelial cells. The objectives of this study were to define the role of KGF and its receptor (KGFR) in rat lung regeneration after trilobectomy and the effect of exogenous KGF expression gene transfection.Methods : Adult Lewis rats were used. Right trilobectomy was performed in operation group and sham thoracotomy in sham group. In operation group, KGF-FLAG or FLAG expression vector was transfected directly to the lung by electroporation. KGF, KGFR expression, and alveolar cell proliferation index using proliferating cell nuclear antigen (PCNA) were measured in the right lung at 14 days after operation.Results : PCNA, KGF and KGFR expressions in lung epithelial cells were significantly increased at day 4 after trilobectomy. Transfection of KGF-FLAG expression vector resulted in further significant enhancements of PCNA at day 4 after trilobectomy ; however, the transfection of FLAG expression vector did not alter the enhancement of PCNA. Exogenous expression of KGF in the remaining lung by electroporation significantly augmented epithelial proliferation.Conclusion : Our results implicate KGF in the induction of alveolar epithelial cell proliferation for compensatory regeneration of lung, and that overexpression of KGF in the remaining lung by electroporation significantly augmented lung epithelial proliferation.