Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed

Unfolded Protein Response and Crohn’s Diseases: A Molecular Mechanism of Wound Healing in the Gut

Version 1 : Received: 22 December 2020 / Approved: 23 December 2020 / Online: 23 December 2020 (09:42:56 CET)
Version 2 : Received: 8 January 2021 / Approved: 12 January 2021 / Online: 12 January 2021 (17:03:10 CET)

A peer-reviewed article of this Preprint also exists.

Li, C. Unfolded Protein Response and Crohn’s Diseases: A Molecular Mechanism of Wound Healing in the Gut. Gastrointest. Disord. 2021, 3, 31-43. Li, C. Unfolded Protein Response and Crohn’s Diseases: A Molecular Mechanism of Wound Healing in the Gut. Gastrointest. Disord. 2021, 3, 31-43.

Journal reference: Gastrointest. Disord. 2021, 3, 4
DOI: 10.3390/gidisord3010004

Abstract

Endoplasmic reticulum (ER) stress triggers a series of signaling and transcriptional events termed the unfolded protein response (UPR). Severe ER stress is associated with the development of fibrosis in different organs including lung, liver, kidney, heart, and intestine. ER stress is an essential response of epithelial and immune cells in the pathogenesis of inflammatory bowel disease (IBD) including Crohn’s disease. Intestinal epithelial cells are susceptible to ER stress-mediated damage due to secretion of a large amount of proteins that are involved in mucosal defense. In other cells, ER stress is linked to myofibroblast activation, extracellular matrix production, macrophage polarization, and immune cell differentiation. This review focuses on the role of UPR in the pathogenesis in IBD from an immunologic perspective. The roles of macrophage and mesenchymal cells in the UPR from in vitro and in vivo animal models are discussed. The links between ER stress and other signaling pathways such as senescence and autophagy are introduced. Recent advances in the understanding of the epigenetic regulation of UPR signaling are also updated here. The future directions of development of the UPR research and therapeutic strategies to manipulate ER stress levels are also reviewed.

Subject Areas

Unfolded protein response; Endoplasmic reticulum stress; Glucose-regulated protein 78 kD; Inflammatory Bowel Diseases; Crohn’s disease; Fibrosis; Wound healing

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