Fibroblast growth factor 10 alleviates acute lung injury by inhibiting excessive autophagy via Nrf2.

Acute lung injury (ALI) is associated with an increased incidence of respiratory diseases, which are devastating clinical disorders with high global mortality and morbidity. Evidence confirms that fibroblast growth factors (FGFs) play key roles in mediating ALI. Mice were treated with LPS (lipopolysaccharide: 5 mg/kg, intratracheally) to establish an in vivo ALI model. Human lung epithelial BEAS-2B cells cultured in a corresponding medium with LPS were used to mimic the ALI model in vitro. In this study, we characterized FGF10 pretreatment (5 mg/kg, intratracheally) which improved LPS-induced ALI, including histopathological changes, and reduced pulmonary edema. At the cellular level, FGF10 pretreatment (10 ng/mL) alleviated LPS-induced ALI accompanied by reduced reactive oxygen species (ROS) accumulation and inflammatory responses, such as IL-1ß, IL-6, and IL-10, as well as suppressed excessive autophagy. Additionally, immunoblotting and co-immunoprecipitation showed that FGF10 activated nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway via Nrf2 nuclear translocation by promoting the interaction between p62 and keap1, thereby preventing LPS-induced ALI. Nrf2 knockout significantly reversed these protective effects of FGF10. Together, FGF10 protects against LPS-induced ALI by restraining autophagy via p62-Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 signaling pathway, implying that FGF10 could be a novel therapy for ALI.

Association of oxidative balance score and lung health from the National Health and Nutrition Examination Survey 2007-2012.

Background: Oxidative stress is associated with outcomes of chronic lung disease. The oxidative stress-related exposures of diet and lifestyle can be evaluated by the oxidative balance score (OBS), and higher OBS scores indicate more significant antioxidant exposures. But the relationship between OBS and lung health is unknown. Purpose: The aim of this study was to explore the association between OBS and lung health (respiratory symptoms, chronic lung disease, and lung function). Methods: A series of models, including weighted linear models, weighted logistic regression, and weighted multinomial logistic regression, were performed to assess the associations of OBS with respiratory symptoms, chronic lung disease, and lung function. The models adjusted by age, race/ethnicity, gender, educational background, poverty-to-income ratio, and dietary energy were also performed. Results: Cross-sectional data of 5,214 participants from the National Health and Nutrition Examination Survey for the years 2007-2012 were analyzed. For every one-unit increase in OBS, the odds of wheezing/chronic bronchitis decreased by 6%. Increased OBS was associated with higher percent-predicted forced expiratory volume in one second (FEV1) (adjusted mean difference (MD), 0.21%; 95% CI: 0.10-0.32) and percent-predicted forced vital capacity (FVC) (adjusted MD, 0.15%; 95% CI: 0.07-0.24). A significantly lower risk of wheezing/chronic bronchitis was found in participants in the second/third/fourth OBS quartile compared to those in the first OBS quartile (all P for trend < 0.05). Moreover, higher percent-predicted FEV1 and FVC were also found in the third quartile and fourth quartile (all P for trend < 0.05). Furthermore, both dietary and lifestyle components were tightly related to pulmonary outcomes. Many associations were maintained after stratified by sex or after sensitivity analyses. Conclusion: Oxidative balance score was negatively correlated with the diagnosis of chronic bronchitis/wheezing/restrictive spirometry pattern and positively correlated with percent-predicted FVC and FEV1. It seems that the higher the OBS score, the better the pulmonary outcomes. The findings highlight the importance of adherence to an antioxidant diet and lifestyle and that it contributes to lung health.