Role of binding immunoglobulin protein (Bip) in graves’ orbitopathy pathogenesis

Jaesang Ko, Ji Young Kim, Eun Jig Lee, Jin Sook Yoon

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Inflammation and adipogenesis represent the main pathogenic mechanisms of Graves’ orbitopathy (GO), and oxidative stress is a well-known inducer of GO pathology. Endoplasmic reticulum (ER) stress has been suggested as a major contributor to inflammation and reactive oxygen species (ROS) generation. In this study, we investigated the role of the ER-stress chaperone protein, binding immunoglobulin protein (BiP), in GO pathogenesis. Using primary cultures of orbital fibroblasts from patients with GO, we examined the role of BiP in GO pathogenesis by silencing its expression with small-interfering RNA (siRNA). Inflammatory cytokine expression was analysed by Western blotting and ELISA. Intracellular ROS levels induced by hydrogen peroxide or cigarette smoke extract were measured by 5-(and 6)-carboxy-20,70-dichlorodihydrofluorescein diacetate staining and flow cytometry. After adipogenic differentiation in BiP siRNA-transfected cells, the cells were stained with Oil Red O, and the levels of adipogenic transcription factors were determined by Western blot analysis. BiP mRNA expression levels were significantly higher in GO orbital tissues than in non-GO orbital tissues. Silencing BiP attenuated the expression of pro-inflammatory cytokines (interleukin-6, intercellular adhesion molecule-1, and monocyte chemotactic protein-1) in primary cultured GO orbital fibroblasts. Silencing BiP also reduced ROS generation, hyaluronan production, and adipocyte differentiation. These findings suggest that ER stress is involved in the aetiology of GO and that modulation of ER stress has therapeutic potential for GO.

Original languageEnglish
Pages (from-to)71-81
Number of pages11
JournalJournal of molecular endocrinology
Volume66
Issue number1
DOIs
Publication statusPublished - 2021 Jan

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (grant number NRF-2020R1C1C1004081).

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and 阀CT (grant number NRF-2020R1C1C1004081).

Publisher Copyright:
© 2021 Society for Endocrinology Published by Bioscientifica Ltd.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

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