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The Role of SIRT1 in Autophagy in Lipopolysaccharide-Induced Mouse Type II Alveolar Epithelial Cells

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Abstract

Silent mating type information regulation 2 homolog-1 (SIRT1) is involved in a wide range of cellular processes because of its role as a deacetylated histone and its association with a variety of transcription factors. SIRT1 has essential roles in autophagy, including in the formation of autophagic vacuoles and the assembly of autophagy-related gene (ATG) protein complexes. The present study focused on the role of SIRT1 in autophagy in lipopolysaccharide (LPS)-induced mouse type II alveolar epithelial cells (AECII). We designed experiments using SIRT1-overexpressing mice and wild-type mice, and AECII were isolated from these two types of mouse for in vitro LPS injury trials. Our results suggest that levels of the autophagy proteins, Beclin1 and LC3B, as well as those of the inflammatory factors, IL-6 and TNF-α, were increased in LPS-induced mouse AECII, and that SIRT1 protected against damage in mice with acute respiratory distress syndrome and in mouse AECII in vitro following LPS treatment. Subsequently, we screened multiple inflammatory, apoptotic, and unclassified genes (including Atg7), which interacted with SIRT1 in LPS-injured mouse AECII, as assessed by mRNA microarray analysis. These results demonstrate that LPS can reduce the levels of SIRT1 and ATG7 in vivo and in vitro and indicate that SIRT1 is involved in autophagy through regulation of ATG7 in AECII in response to LPS.

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Abbreviations

SIRT1:

silent mating type information regulation 2 homolog-1

ARDS:

acute respiratory distress syndrome

HDACs:

histone deacetylases

NAD+:

nicotinamide adenine dinucleotide

AECII:

type II alveolar epithelial cells

LPS:

lipopolysaccharide

SP-C:

surfactant-associated protein C

IL-6:

interleukin-6

TNF-α:

tumor necrosis factoralpha

HE:

hematoxylin and eosin

ATG7:

autophagy-related gene protein 7

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Funding

This study was supported by The National Natural Science Fund, China (81370167).

Author information

Author notes

  1. Junyan Liu and Xuejun Lv contributed equally to this work.

Authors and Affiliations

  1. Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China

    Junyan Liu, Weijie Dong, Mingdong Hu, Jiancheng Xu, Guisheng Qian & Yuying Li

  2. Respiratory department of the No.88th Hospital, Taian, 271000, Shandong, China

    Xuejun Lv

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  1. Junyan Liu
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  2. Xuejun Lv
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  4. Mingdong Hu
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  7. Yuying Li
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Correspondence to Yuying Li.

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The authors declare that they have no conflict of interest.

Ethical Approval

All animal experiments were conducted in accordance with National Guidelines for the Care and Use of Laboratory Animals and were authorized by the Third Military Medical University Bioethics Committee.

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Liu, J., Lv, X., Dong, W. et al. The Role of SIRT1 in Autophagy in Lipopolysaccharide-Induced Mouse Type II Alveolar Epithelial Cells. Inflammation 41, 2222–2235 (2018). https://doi.org/10.1007/s10753-018-0865-9

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  • DOI: https://doi.org/10.1007/s10753-018-0865-9

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