期刊
LUNG
卷 195, 期 3, 页码 295-301出版社
SPRINGER
DOI: 10.1007/s00408-017-9997-1
关键词
Alveolar macrophages; CSE; Senescence; Anti-aging protein
资金
- Natural Science Program of Anhui Universities [KJ2017A274]
- [YR201107]
Introduction Chronic obstructive pulmonary disease is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a fundamental cellular process that eliminates long-lived proteins and damaged organelles through lysosomal degradation pathway, though its role in human diseases remains unclear. We hypothesized that an anti-aging protein, Klotho plays an important role in regulating autophagy in response to cigarette smoke (CS). Methods Autophagy was measured by detecting LC3-I and LC3-II expressions. The regulation of autophagy expression by cigarette smoke extract (CSE) was studied in vitro, and small-interfering RNA (siRNA) and recombinant Klotho were employed to investigate the role of Klotho on CSE-induced autophagy. Protein levels and phosphorylation were measured by Western blot assay. Results CS exposure resulted in induction of autophagy in alveolar macrophages. Pretreatment of cells with Klotho attenuated CS-induced autophagy whereas knockdown of Klotho augmented CS-induced autophagy. Klotho inhibited phosphorylation of ERK, Akt, and IGF-1 in CSE-stimulated cells. Conclusions These data suggest that Klotho plays a critical role in the regulation of CS-induced autophagy and have important implications in understanding the mechanisms of CS-induced cell death and senescence.
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