The early and late intervention effects of collagen-binding FGF2 on elastase-induced lung injury

Abstract

IntroductionChronic obstructive pulmonary disease (COPD) has high morbidity and mortality, with no effective treatment at present. Emphysema, a major component of COPD, is a leading cause of human death worldwide. Fibroblast growth factor 2 (FGF2) is implicated in the pathogenesis of pulmonary emphysema and may play an important role in the lung repair process after injury, but concerns remain with respect to its effectiveness. ObjectiveIn the present work, we sought to determine how the timing (early and late intervention) of sustained-release FGF2 system administration impacted its effectiveness on a porcine pancreatic elastase (PPE)-induced lung injury mouse model. MethodsTo examine the early intervention efficiency of collagen-binding FGF2 (CBD-FGF2), mice received intratracheally nebulized CBD-FGF2 with concurrent intratracheal injection of PPE. To explore the late intervention effect, CBD-FGF2 was intratracheally aerosolized after PPE administration, and lungs were collected after CBD-FGF2 treatment for subsequent analysis. ResultIn response to PPE, mice had significantly increased alveolar diameter, collagen deposition and expression of inflammatory factors and decreased lung function indices and expression of alveolar epithelium markers. Our results indicate that CBD-FGF2 administration was able to prevent and repair elastase-induced lung injury partly through the suppression of the inflammatory response and recovery of the alveolar epithelium. The early use of CBD-FGF2 for the prevention of PPE-induced emphysema showed better results than late therapeutic administration against established emphysema. ConclusionThese data provide insight regarding the prospective role of a drug-based option (CBD-FGF2) for preventing and curing emphysema.