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

角质形成细胞生长因子是肺叶切除术后肺代偿再生的有效调节剂

• 批准号: 16591402
• 负责人: NAGAYASU Takashi
• 金额: $ 2.24万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591402/
• 关键词: Keratinocyte growth factor; regeneration of lung and bronchus; gene therapy; Keratinocyto growth factor; 肺再生; 気管支再生; Electroporation; Gene therapy

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.

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。角质细胞生长因子（KGF）在肺组织中表达，被认为是肺上皮细胞的可能的促分裂原。本研究的目的是明确KGF及其受体（KGFR）在大鼠三叶切除术后肺再生中的作用以及外源性KGF表达基因转染的影响。手术组行右三叶切除术，假手术组行假开胸术。手术组采用电穿孔法将KGF-FLAG或FLAG表达载体直接转染至肺组织。结果：术后第4天，肺上皮细胞PCNA、KGF、KGFR表达均明显增加，肺组织中KGF、KGFR表达均明显高于术前，肺组织中KGF、KGFR表达均明显高于术后第14天。转染KGF-FLAG表达载体后，在术后第4天，PCNA表达进一步增强，但转染FLAG表达载体后，PCNA的表达没有改变。外源性表达的KGF在剩余的肺通过电穿孔显着增强epithelial proliferation.Conclusion：我们的研究结果牵连KGF在诱导肺泡上皮细胞增殖肺的代偿性再生，和过度表达的KGF在剩余的肺通过电穿孔显着增强肺上皮细胞增殖。