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

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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.