P-152 Increased ER Stress and Unfolded Protein Response in Subepithelial Myofibroblasts Contributes to Fibrosis in Crohnʼs Disease

Li, Chao; Kuemmerle, Jay

doi:10.1097/01.mib.0000480248.94772.21

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“…ER stress response with the feature of GRP78, XBP1s and ATF6α over-expression can be also activated in the normal mesenchymal cells when treated with tunicamycin. 64,65 The increased amount of ER stress in affected ileum was found to be associated with increased silencing of microRNA (miR)-199a-5p by DNMT1-mediated promoter hypermethylation. 64,65 In the at-rest condition, miR-199a-5p targets different ER stressors including GRP78, ATF6 and XBP1s for their degradation 64,65 (Fig.…”

Section: Er Stress Crohn's Disease Intestinal Inflammation and Immumentioning

confidence: 99%

The Role of Endoplasmic Reticulum Stress in the Development of Fibrosis in Crohn’s Disease

Li¹

2018

Exploratory Research and Hypothesis in Medicine

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When cells are subject to endoplasmic reticulum (ER) stress due to inflammation, inadequate nutrition or infection, a characteristic environment of glucose starvation, acidosis and hypoxia is created. All the conditions cited contribute to ER stress as well as the unfolded protein response (UPR). The UPR is active in a variety of human tumor types. Depending on the severity of ER stress, the UPR can exert a cytoprotective function by resolving the misfolded or unfolded protein, further reducing the ER protein load in mild stress, or by sending signal to cells to undergo cell death by apoptosis in the severe condition. Recent studies suggest that the glucose-regulated protein (GRP)78, or immunoglobulin heavy chain binding protein (BiP), not only confers an advantage to cell survival through an anti-apoptotic function but also may improve cell proliferation and angiogenesis. Understanding how the UPR can induce adaptation to chronic stress instead of apoptosis in cells will be of invaluable significance toward finding a cure for ER stress-associated diseases. This review covers what is known about the adaptive responses of cells when facing ER stress and how these information may lead to discoveries of novel treatments for various related disorders. Studies have suggested that ER stress promotes tissue remodeling under a variety of conditions and through several mechanisms, including activation of apoptosis, epithelialmesenchymal transition, and enhanced inflammatory response. This review also focuses on the major cell components in the gut, primarily epithelial cells and mesenchymal cells, for which a myriad of evidence suggests that sustained ER stress causes epithelial cell damage along with resultant mucosal barrier dysfunction, stimulates mesenchymal cell differentiation, and induces myofibroblasts activation and their secretion of excess extracellular protein leading to matrix collagen-rich tissue formation. Several key questions are still not answered by the fibrosis research and are discussed in this review: for example, the mechanisms of ER stress induction and the specific signaling pathway(s) activated by which UPR leads to development of organ fibrosis, or how to maintain ER stress at a basal level instead of exacerbating its physiological role that is otherwise necessary to maintain intracellular homeostasis. Ultimately, further investigations are needed to bridge the gap between our current understanding of ER stress mechanisms and to identify efficient anti-fibrotic therapeutic regimens.

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Section: Er Stress Crohn's Disease Intestinal Inflammation and Immumentioning

confidence: 99%

The Role of Endoplasmic Reticulum Stress in the Development of Fibrosis in Crohn’s Disease

Li¹

2018

Exploratory Research and Hypothesis in Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

P-152 Increased ER Stress and Unfolded Protein Response in Subepithelial Myofibroblasts Contributes to Fibrosis in Crohnʼs Disease

Cited by 1 publication

References 0 publications

The Role of Endoplasmic Reticulum Stress in the Development of Fibrosis in Crohn’s Disease

The Role of Endoplasmic Reticulum Stress in the Development of Fibrosis in Crohn’s Disease

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