Interactions Between Autophagy and the Unfolded Protein Response: Implications for Inflammatory Bowel Disease

Hooper, Kirsty M; Barlow, Peter G; Henderson, Paul; Stevens, Craig

Abstract

Inflammatory Bowel Disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis, is characterised by chronic inflammation of the gastrointestinal tract. Aetiology involves a combination of genetic and environmental factors resulting in abnormal immune responses to intestinal microbiota. Genetic studies have strongly linked genes involved in autophagy to CD, and genes involved in the unfolded protein response (UPR) to IBD. The UPR is triggered in response to accumulation of misfolded proteins in the endoplasmic reticulum (ER) and autophagy plays a key role to relieve ER-stress and restore homeostasis. This review summarises the known interactions between autophagy and the UPR and discusses the impact of these converging pathways on IBD pathogenesis. With a paucity of effective long-term treatments for IBD, targeting of synergistic pathways may provide novel and more effective therapeutic options.

• Journal Article Type: Review
• Acceptance Date: Nov 14, 2018
• Online Publication Date: Dec 24, 2018
• Publication Date: 2019-04
• Deposit Date: Jan 10, 2019
• Publicly Available Date: Jan 10, 2019
• Journal: Inflammatory Bowel Diseases
• Print ISSN: 1078-0998
• Electronic ISSN: 1536-4844
• Publisher: Lippincott, Williams & Wilkins
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 4
• Pages: 661-671
• DOI: https://doi.org/10.1093/ibd/izy380
• Keywords: IBD, autophagy, unfolded protein response, ER stress
• Public URL: http://researchrepository.napier.ac.uk/Output/1496406
• Contract Date: Jan 10, 2019