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Published in: Pediatric Surgery International 12/2019

01-12-2019 | Original Article

The role of autophagy in intestinal epithelial injury

Authors: Masaya Yamoto, Carol Lee, Sinobol Chusilp, Yuta Yazaki, Mashriq Alganabi, Bo Li, Agostino Pierro

Published in: Pediatric Surgery International | Issue 12/2019

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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.
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Metadata
Title
The role of autophagy in intestinal epithelial injury
Authors
Masaya Yamoto
Carol Lee
Sinobol Chusilp
Yuta Yazaki
Mashriq Alganabi
Bo Li
Agostino Pierro
Publication date
01-12-2019
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Surgery International / Issue 12/2019
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI
https://doi.org/10.1007/s00383-019-04566-2

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