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Pediatric Surgery International

Published in:

01-10-2020 | Original Article

Lysosomal overloading and necrotizing enterocolitis

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

Published in: Pediatric Surgery International | Issue 10/2020

Abstract

Purpose

Intestinal absorption in premature infants occurs via direct epithelial cellular endocytosis and degradation by intracellular lysosomes. Autophagy is a mechanism by which cytoplasmic organelles contribute to lysosomal degradation. However, excessive autophagy can lead to cell death. The purpose of this study was to investigate whether autophagy and endocytosis are present in the small intestinal mucosa during experimental necrotizing enterocolitis (NEC).

Methods

NEC was induced by gavage feeding of hyperosmolar formula, lipopolysaccharide and hypoxia between P5 and P9 (ethical approval 44032). Breastfed mice were used as control. Distal ileum was harvested on P5, P7 and P9 and analyzed for intestinal epithelial cellular morphology as well as autophagy/lysosomal activity, and cell death. Groups were compared using Student’s t test.

Results

During NEC, giant lysosomes were present in the intestinal villi, with some exceeding their degradation ability leading to their rupture. The NEC group had significantly increased inflammation and autophagy activity, decreased lysosome activity, and increased apoptosis compared to control.

Conclusions

NEC induction causes excessive autophagy and endocytosis leading to lysosomal overloading, lysosomal membrane permeabilization and rupture which results in cell death. These novel findings may help to clarify the pathogenesis of NEC. Reduction of lysosome overload and assisting in their degradation capability may reduce the burden of NEC.

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Title: Lysosomal overloading and necrotizing enterocolitis
Authors: Masaya Yamoto
Mashriq Alganabi
Sinobol Chusilp
Dorothy Lee
Yuta Yazaki
Carol Lee
Bo Li
Agostino Pierro
Publication date: 01-10-2020
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Surgery International / Issue 10/2020
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-020-04724-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Lysosomal overloading and necrotizing enterocolitis

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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