Related Experiment Video

Updated: Jun 23, 2025

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

8.5K

Role of Inositol-Requiring Enzyme 1 and Autophagy in the Pro-Fibrotic Mechanism Underlying Graves' Orbitopathy

Chae Eun Lee1,2, Ji-Young Kim1, Jin Sook Yoon1

  • 1Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea.

Yonsei Medical Journal
|June 24, 2024
PubMed
Abstract

Insights

In Graves' orbitopathy (GO), inositol-requiring enzyme 1 (IRE1) drives fibrosis by mediating endoplasmic reticulum (ER) stress and autophagy. Silencing IRE1 or inhibiting autophagy reduced fibrotic markers, suggesting therapeutic potential.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Molecular Medicine

Background:

  • Orbital fibroblasts are central to Graves' orbitopathy (GO) pathogenesis.
  • Endoplasmic reticulum (ER) stress and autophagy are implicated in GO development.

Purpose of the Study:

  • To investigate the role of inositol-requiring enzyme 1 (IRE1) and associated autophagy in the pro-fibrotic mechanisms of GO.
  • To elucidate the specific contribution of IRE1-mediated pathways to GO.

Main Methods:

  • Orbital adipose/connective tissues from GO patients and controls were analyzed.
  • GO fibroblasts were treated with IRE1 small-interfering RNA and bafilomycin A1 (Baf-A1).
  • Protein expression was assessed via western blotting following transforming growth factor (TGF)-β stimulation.

Main Results:

  • Transforming growth factor-β (TGF-β) upregulated IRE1 in GO fibroblasts.
  • Silencing IRE1 inhibited both fibrosis and autophagy.
  • Bafilomycin A1 (Baf-A1), an autophagy inhibitor, reduced pro-fibrotic protein expression.

Conclusions:

  • Inositol-requiring enzyme 1 (IRE1) is a key mediator of autophagy and fibrosis in Graves' orbitopathy.
  • These findings offer a deeper understanding of GO pathogenesis.
  • IRE1 and autophagy pathways represent potential therapeutic targets for GO.
Keywords:
AutophagyGraves' orbitopathyendoplasmic reticulum stressfibrosisinositol-requiring enzyme 1thyroid eye disease

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