IL-17A regulates collagen synthesis after autophagy in bronchial fibroblasts through the PI3K/AKT/mTOR pathway

Abstract

Abstract Background Airway inflammation and remodeling are the most important characteristics of COPD. Our previous studies have shown that airway inflammation in COPD is related to upregulation of IL-17A, but the relationship with airway remodeling still needs further investigation. It is speculated that IL-17A can regulate autophagy of bronchial fibroblasts and affect collagen production, exacerbating airway remodeling. This article aims to explore the mechanism of IL-17A regulating the autophagy pathway PI3K/Akt/mTOR in COPD airway remodeling at the cellular level. Targeting IL-17A therapy may provide new ideas for the treatment of COPD airway remodeling. Methods Primary bronchial fibroblasts isolated from Sprague-Dawley (SD) rats were treated with IL-17A, rapamycin, Ly294002 (a PI3K-Akt inhibitor), or IL-17A+rapamycin.Western blotting was used to detect the expression of autophagic markers (LC3 and p62), PI3K, mTOR and AKT. Transmission electron microscopy (TEM) was used to observe the changes in the number of autophagosomes (APs) in the cells in each group. Western blotting (WB) and immunofluorescence (IF) analysis were used to detect changes in the protein expression levels of Collagen I and Collagen III in each group. Results Our results suggested that IL-17A activated PI3K/AKT/mTOR signaling and inhibited autophagy in bronchial fibroblasts by inhibiting autophagosome formation. We also observed that IL-17A promoted collagen production by inhibiting bronchial fibroblast autophagy. Our findings indicated that modulators of autophagy may be developed as new therapeutic target for COPD by repressing airway remodeling. Conclusions IL-17A promotes the synthesis of Collagen I and Collagen III in bronchial fibroblasts by inhibiting autophagy via activation of the PI3K-Akt-mTOR pathway. Conclusions IL-17A promotes the synthesis of Collagen I and Collagen III in bronchial fibroblasts by inhibiting autophagy via activation of the PI3K-Akt-mTOR pathway.