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

Abstract

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 adapted treatment with LPS (lipopolysaccharide; 5 mg/kg, intratracheally) to establish in vivo ALI model. Human lung epithelial BEAS-2B cells cultured in a corresponding medium with LPS were performed to mimic ALI model in vitro. In this study, we characterized FGF10 pretreatment (5 mg/kg, intratracheally) 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-1β, 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.

Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway

“…23,24 Studies have shown that inhibiting LPS-induced excessive autophagy in alveolar epithelial cells can mitigate inflammatory injury. 25,26 Moreover, excessive autophagy activation has been implicated in the development of ALI, [27][28][29][30] and the effective inhibition of autophagy is a potential therapeutic approach. Thus, modulating autophagy from inducing death to supporting survival could prove effective in the treatment of LPS-induced ALI.…”