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Related Concept Videos

Inflammatory Bowel Disease III: Crohn's Disease01:25

Inflammatory Bowel Disease III: Crohn's Disease

Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
Inflammatory Bowel Disease II: Ulcerative Colitis01:20

Inflammatory Bowel Disease II: Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by continuous mucosal inflammation that typically begins in the rectum and extends proximally in a uniform pattern. Its pathogenesis involves a complex interplay of genetic predisposition, immune dysregulation, and environmental influences. These factors converge to impair the colon’s epithelial defenses and promote an exaggerated inflammatory response against luminal contents.Breakdown of the Mucosal BarrierA...
Irritable Bowel Syndrome I: Introduction01:17

Irritable Bowel Syndrome I: Introduction

Irritable Bowel Syndrome (IBS) is characterized by functional disturbances in the gastrointestinal system, presenting a cluster of symptoms without evident structural or biochemical abnormalities. It primarily affects the large intestine and may cause abdominal pain, bloating, excessive gas, diarrhea, constipation, or both.
IBS is a chronic condition that can persist over a long period or recur frequently.
The pathogenesis of IBS involves a complex interplay of the following factors:
Altered...
Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Inflammatory Bowel Disease II: Crohn's Disease01:30

Inflammatory Bowel Disease II: Crohn's Disease

Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by transmural...

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A TNBS-Induced Rodent Model to Study the Pathogenic Role of Mechanical Stress in Crohn's Disease
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Endoplasmic reticulum stress: implications for inflammatory bowel disease pathogenesis.

Arthur Kaser1, Eduardo Martínez-Naves, Richard S Blumberg

  • 1Department of Medicine II (Gastroenterology & Hepatology), Innsbruck Medical University, Innsbruck, Austria.

Current Opinion in Gastroenterology
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Cellular stress responses, particularly the unfolded protein response (UPR), play a critical role in inflammatory bowel disease (IBD) pathogenesis. Disruptions in the UPR pathway contribute to intestinal inflammation, highlighting a new therapeutic target for IBD.

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Area of Science:

  • Gastroenterology
  • Cell Biology
  • Immunology

Background:

  • Inflammatory bowel disease (IBD) involves chronic intestinal inflammation.
  • Cellular stress responses are increasingly recognized as key players in IBD.

Purpose of the Study:

  • To review the emerging role of cellular stress responses in IBD.
  • To highlight the unfolded protein response (UPR) as a critical pathway.

Main Methods:

  • Literature review of cellular stress pathways in IBD.
  • Focus on the unfolded protein response (UPR) and endoplasmic reticulum (ER) stress.

Main Results:

  • The UPR is essential for intestinal cell homeostasis, especially in secretory cells like Paneth and goblet cells.
  • Genetic defects in UPR components (e.g., XBP1, ARG2, ORMDL3) and related proteins (e.g., MUC2, HLAB27) are implicated in IBD.
  • Environmental factors (microbial products, cytokines) can disrupt UPR, promoting intestinal inflammation.

Conclusions:

  • Endoplasmic reticulum stress is a significant pathway in the development of IBD.
  • This pathway may also be involved in other intestinal inflammatory disorders.