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Review
. 2025 Feb;241(2):e14284.
doi: 10.1111/apha.14284.

Unfolded protein response: An essential element of intestinal homeostasis and a potential therapeutic target for inflammatory bowel disease

Miriam Di Mattia  1   2 , Michele Sallese  1   2 , Loris Riccardo Lopetuso  1   2   3
Affiliations
Review

Unfolded protein response: An essential element of intestinal homeostasis and a potential therapeutic target for inflammatory bowel disease

Miriam Di Mattia et al. Acta Physiol (Oxf). 2025 Feb.

Abstract

Different physiological and pathological situations can produce alterations in the cell's endoplasmic reticulum (ER), leading to a condition known as ER stress, which can trigger an intricate intracellular signal transduction system known as the unfolded protein response (UPR). UPR is primarily tailored to restore proteostasis and ER equilibrium; otherwise, if ER stress persists, it can cause programmed cell death as a cytoprotective mechanism and drive inflammatory processes. Therefore, since intestinal cells strongly rely on UPR for their biological functions and unbalanced UPR has been linked to inflammatory, metabolic, and immune disorders, here we discussed the role of the UPR within the intestinal tract, focusing on the UPR contribution to inflammatory bowel disease development. Importantly, we also highlighted the promising potential of UPR components as therapeutic targets for intestinal inflammatory diseases.

Keywords: ER stress; IBD; KDEL receptors; autophagy; inflammation; molecular chaperones; proteostasis.

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References

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