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

Journal Article · Sun Apr 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.03.039· OSTI ID:23137226

Gui, Xianhua ^[1]; Chen, Hongwei ^[2]; Cai, Hourong ^[1]; Sun, Lingyun ^[3]; Gu, Luo ^[4]

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1. Department of Respiratory Medicine, The Affiliated Nanjing Drum Tower clinical medical college of Nanjing Medical University, 210008, Nanjing (China)
2. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, 210008, Nanjing (China)
3. Department of Rheumatology and Immunology, The Affiliated Nanjing Drum Tower Clinical Medical College of Nanjing Medical University, 210008, Nanjing (China)
4. Department of Physiology of Nanjing Medical University, 211166, Nanjing (China)

Highlights: • Leptin expression is associated with the severity of IPF. • Leptin accelerated the TGF-β1 induced epithelial mesenchymal transition of A549 cells. • The pro-fibrogenic effects of leptin occurred through 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 diseases 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 leptin on fibrosis in TGF-β1 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 α-SMA production. Additionally, treatment with leptin decreased autophagosome formation, inhibited the lipidation 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.

• OSTI ID: 23137226
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 498; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOLOGICAL FUNCTIONS
COLLAGEN
FIBROSIS
GENES
LEPTIN
LUNGS
METABOLIC DISEASES
PATHOGENESIS