Abstract
Preservation or restoration of normal alveolar epithelial barrier function is crucial for pulmonary oedema resolution. Keratinocyte growth factor-2 (KGF-2), a potent epithelial cell mitogen, may have a role in preventing ventilator-induced lung injury (VILI), which occurs frequently in mechanically ventilated patients. The aim of the study was to test the role of KGF-2 in VILI in rats. Forty healthy adult male Sprague-Dawley rats were randomly allocated into four groups, where rats in Groups HVZP (high-volume zero positive end-expiratory pressure) and HVZP+KGF-2 were given intratracheally equal PBS and 5 mg/kg KGF-2 72 hrs before 4 hrs HVZP ventilation (20 ml/kg), respectively, while PBS and KGF-2 were administered in the same manner in Groups Control and KGF-2, which underwent tracheotomy only with spontaneous breathing. Inflammatory cytokines (tumour necrosis factor-α, macrophage inflammatory protein 2), neutrophil and total protein levels in bronchoalveolar lavage fluid and surfactant protein mRNA expression in lung tissue were detected; the number of alveolar type II cells, lung water content and lung morphology were also evaluated. The results indicate that pre-treatment with KGF-2 showed dramatic improvement in lung oedema and inflammation compared with HVZP alone, together with increased surfactant protein mRNA and alveolar type II cells. Our results suggest that KGF-2 might be considered a promising prevention for human VILI or other acute lung injury diseases.
Highlights
Mechanical ventilation is the main life-sustaining tool in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), but unequivocal evidence from both experimental and clinical researches has suggested that mechanical ventilation could aggravate or even initiate lung injury, which is known as ventilation-induced lung injury (VILI) [1]
Keratinocyte growth factor-2 (KGF-2), namely fibroblast growth factor-10 (FGF-10), has been reported to mediate epithelial–mesenchymal interactions, which is essential for lung development [4,5,6,7,8,9,10], and recently it has been found that it may be implicated in preventing lung injury from various stresses [11,12,13]
For surfactant protein C (SP-C). (A) control group: Normal rat lung histologic section after intratracheal administration of PBS; (B) KGF-2 group: Marked alveolar type II cell (ATII) hyperplasia is seen after intratracheal administration of KGF-2; (C) HVZP group: alveolar type II cell decreased in lungs subjected to an injurious ventilatory strategy; (D)
Summary
Mechanical ventilation is the main life-sustaining tool in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), but unequivocal evidence from both experimental and clinical researches has suggested that mechanical ventilation could aggravate or even initiate lung injury, which is known as ventilation-induced lung injury (VILI) [1]. Ventilator-induced lung injury is characterized by increased endothelial and epithelial permeability and inflammatory processes [3]. Keratinocyte growth factor-2 (KGF-2), namely fibroblast growth factor-10 (FGF-10), has been reported to mediate epithelial–mesenchymal interactions, which is essential for lung development [4,5,6,7,8,9,10], and recently it has been found that it may be implicated in preventing lung injury from various stresses [11,12,13]. With similarities to KGF, KGF-2 is a 20-kD heparin-binding protein predominantly expressed by mesenchymal cells. It binds with high affinity to spliced variants of FGF receptor 2-IIIb (FGFR2-IIIb) and FGFR1III-b that are expressed by epithelial and endothelial cells. Unlike KGF, KGF-2 binds to FGFR1III-b [7, 14,15,16,17], which may explain the severely impaired lung development of FGF-10 null mice. The cooperation of FGFR1IIIb and FGFR2IIIb plays an important role in maintaining a 2014 The Authors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
