Protective Effects of Keratinocyte Growth Factor-2 on Ischemia-Reperfusion-Induced Lung Injury in Rats

Ischemia-reperfusion (I/R) is a common cause to compromise tissue injury via endothelial and epithelial barrier dysfunction and damage. Keratinocyte growth factor (KGF)-2 could play an important role in the repair of alveolar epithelial damage and maintain the capillary barrier function. The present study aimed to investigate the potential effects of KGF-2 on I/R-induced lung injury in rats and the related mechanisms. KGF-2 (2.5-10 mg/kg) was administered intratracheally in rats 3 days before the left lobe with ischemia for 60 minutes followed by reperfusion for 180 minutes. Lung injury was evaluated by measuring lung morphology, blood gas analysis, total cell number, and protein concentration in the bronchoalveolar lavage fluid. The protective effects of KGF-2 on human pulmonary microvascular endothelial cells and related mechanisms were evaluated. Pretreatment with KGF-2 significantly prevented I/R-induced lung edema, inflammatory cell infiltration, protein exudation, and the release of inflammatory cytokines in rats, or I/R-induced endothelial cell apoptosis, migration, and barrier dysfunction. Phosphoinositide 3-kinase or epidermal growth factor receptor inhibitors attenuated the protective effect of KGF-2 in endothelial cells. Our results evidence that the local administration of KGF-2 may be an alternative to prophylactic or adjunct drug therapies for I/R-induced lung injury.