Leptin promotes pulmonary fibrosis development by inhibiting autophagy via PI3K/Akt/mTOR pathway

Leptin, a protein-related product of the obesity gene, plays an important role in the pathogenesis of fibrotic diseaies including pulmonary fibrosis. As a highly conservative process, autophagy regulates various biological functions. Otherwise, insufficient autophagy has been described in alveolar epithelial cells (AEC) to cope with the progression of pulmonary fibrosis. Hence, this study is to investigate the effects of leptirion fibrosis in TGF-beta 1 induced epithelial mesenchymal transition (EMT) and the potential roles of autophagy in this processes. Our results showed that the elevated leptin level in serum correlated with the severity of lung fibrosis and leptin significantly promoted the EMT in A549 cells as evidenced by promoting collagen I and alpha-SMA production. Additionally, treatment with leptin decreased autophagosome formation, inhibited the lipidatian of LC3I to LC3II, and up-regulated the expression of p62 via activating PI3K/Akt/mTOR pathway, which is indicative of inhibition of autophagy by leptin. Finally. rapmycin pretreatment reversed the pro-fibrogenic effects of leptin. Taken together, our study suggested that leptin accelerated the EMT of A549 cells through inhibiting autophagy via PI3K/Akt/mTOR pathway. (C) 2018 Elsevier Inc. All rights reserved.