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Klotho Regulates Cigarette Smoke-Induced Autophagy: Implication in Pathogenesis of COPD

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Abstract

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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Acknowledgements

We thank Yujie Wang for technical assistance and Xin Yao for helpful discussion and assistance.

Funding

This study was funded by the Introduction of Talent (YR201107) and the Natural Science Program of Anhui Universities (No. KJ2017A274) .

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    Authors and Affiliations

    1. Department of Respiratory Medicine, Yijishan Hospital, Wannan Medical College, Wuhu, China

      Lingling Li, Liqin Zhang, Yusheng Cheng, Xiongwen Tu & Zhiwei Lu

    2. Department of Emergency, Yijishan Hospital, Wannan Medical College, Wuhu, China

      Min Zhang

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    1. Lingling Li
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    2. Min Zhang
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    Correspondence to Lingling Li or Zhiwei Lu.

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    The authors have no conflicts of interest to report. The authors alone are responsible for the content and writing of the paper.

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    This article does not contain any studies with human participants or animals performed by any of the authors.

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    Informed consent was obtained from all individual participants included in the study.

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    Lingling Li, Min Zhang and Liqin Zhang have contributed equally to this work.

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    Li, L., Zhang, M., Zhang, L. et al. Klotho Regulates Cigarette Smoke-Induced Autophagy: Implication in Pathogenesis of COPD. Lung 195, 295–301 (2017). https://doi.org/10.1007/s00408-017-9997-1

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    • DOI: https://doi.org/10.1007/s00408-017-9997-1

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