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Pediatric Surgery International

, Volume 35, Issue 12, pp 1389–1394 | Cite as

The role of autophagy in intestinal epithelial injury

  • Masaya Yamoto
  • Carol Lee
  • Sinobol Chusilp
  • Yuta Yazaki
  • Mashriq Alganabi
  • Bo Li
  • Agostino PierroEmail author
Original Article
  • 60 Downloads

Abstract

Purpose

Autophagy is a natural mechanism aimed to degrade and recycle cellular components within cells. Previous studies reported that autophagy in the intestinal epithelium can be activated and that excessive autophagy can have negative consequences. However, the mechanism by which autophagy is regulated during intestinal epithelial injury remains unclear. This study aimed to investigate the mechanism of autophagy regulation during intestinal epithelial cells (IEC) injury.

Methods

Rat IEC18 were exposed to hypoxia and Lipopolysaccharide (LPS) (200 μg/ml) to induce injury. IEC18 were treated with autophagy initiation inhibitor, Wortmannin or with autophagy degradation inhibitor, Bafilomycin A1 were added for 24 h. We assessed the number and diameter of autophagic vacuoles, Cell viability, inflammation and apoptosis.

Results

Hypoxia and LPS administration increased the number and diameter of autophagic vacuoles in IEC18. Wortmannin administration reduced the number and diameter of autophagic vacuoles. On the contrary, Bafilomycin A1 administration increased the number of autophagic vacuoles. Cell viability increased following administration of Wortmannin and decreased following administration of Bafilomycin A1.

Conclusions

We found that accumulation of autophagic vacuoles which characterize excessive or incomplete autophagy was detrimental to cell survival. This was shown by an increase in the number and size of the autophagic vacuoles with Bafilomycin A1treatment after hypoxia and LPS stressors relative to hypoxia and LPS alone. Conversely, there was a decrease in the number of autophagic vacuoles with Wortmannin treatment after hypoxia and LPS stressors relative to hypoxia and LPS alone. Therefore, reducing autophagosomes accumulation may represent a novel therapeutic strategy for intestinal injury.

Keywords

Autophagy Intestinal injury Wortmannin Bafilomycin A1 

Notes

Acknowledgements

AP is supported by a Canadian Institutes of Health Research (CIHR) Foundation Grant 353857 and is the Robert M. Filler Chair of Surgery, The Hospital for Sick Children (HSC).

Author contributions

MY: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript. CL, SC, YY, MA, BL: collection and/or assembly of data, data analysis and interpretation, final approval of manuscript. AP: conception and design, financial support, final approval of manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Masaya Yamoto
    • 1
    • 2
  • Carol Lee
    • 1
  • Sinobol Chusilp
    • 1
    • 3
  • Yuta Yazaki
    • 1
  • Mashriq Alganabi
    • 1
  • Bo Li
    • 1
  • Agostino Pierro
    • 1
    • 4
    Email author
  1. 1.Division of General and Thoracic Surgery, Translational Medicine ProgramThe Hospital for Sick ChildrenTorontoCanada
  2. 2.Department of Pediatric SurgeryShizuoka Children’s HospitalShizuokaJapan
  3. 3.Division of Pediatric Surgery, Department of SurgeryKhon Kaen UniversityKhon KaenThailand
  4. 4.Division Head, Pediatric Surgery, Robert M. Filler Professor of SurgeryUniversity of TorontoTorontoCanada

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