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Endoplasmic reticulum stress in the acute intestinal epithelial injury of necrotizing enterocolitis

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Abstract

Endoplasmic reticulum (ER) is a dynamic organelle that has many functions including protein synthesis, lipid synthesis, and calcium metabolism. Any perturbation in the ER such as accumulation of unfolded or misfolded proteins in the ER lumen causes ER stress. ER stress has been implicated in many intestinal inflammatory diseases. However, the role of ER stress in acute intestinal epithelial injuries such as necrotizing enterocolitis in preterm neonates, remains incompletely understood. In this review, we introduce ER structure, functions and summarize the intracellular signaling pathways involved in unfolded protein response (UPR), a survival mechanism in which cells exert an adaptive function to restore homeostasis in the ER. However, intense and prolonged ER stress induces apoptotic response which results in apoptotic cell death. We also discuss and highlight recent advances that have improved our understanding of the molecular mechanisms that regulate the ER stress in acute intestinal epithelial injuries such as necrotizing enterocolitis (NEC). We focus on the role of ER stress in influencing gut homeostasis in the neonatal period and on the potential therapeutic interventions to alleviate ER stress-induced cell death in NEC.

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Acknowledgements

This work was supported by Canadian Institutes of Health Research (CIHR) [Foundation Grant number 353857].

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Authors and Affiliations

  1. Division of General and Thoracic Surgery, The Hospital for Sick Children, University of Toronto, 1526-555 University Ave, Toronto, ON, M5G 1X8, Canada

    Ethan Lau, Carol Lee, Bo Li & Agostino Pierro

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  1. Ethan Lau
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  2. Carol Lee
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EL, CL, BL: writing—original draft; AP: conceptualization, supervision, writing—review and editing.

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Correspondence to Agostino Pierro.

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Lau, E., Lee, C., Li, B. et al. Endoplasmic reticulum stress in the acute intestinal epithelial injury of necrotizing enterocolitis. Pediatr Surg Int 37, 1151–1160 (2021). https://doi.org/10.1007/s00383-021-04929-8

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