Signal transducer and activator of transcription 3 as a potential therapeutic target for Graves’ orbitopathy

Jae Sang Ko, Ji Young Kim, Bo Ram Kim, Eun Jig Lee, Don O. Kikkawa, Jin Sook Yoon

Research output: Contribution to journalArticlepeer-review

Abstract

The roles of signal transducer and activator of transcription 3 (STAT3) in inflammation, oxidative stress, and adipogenesis during Graves’ orbitopathy (GO) are incompletely understood. Here, STAT3 expression in orbital tissues (from individuals with GO and healthy control subjects) was studied, and the role of STAT3 in GO pathogenesis was examined through small-interfering RNA (siRNA)-mediated silencing in primary orbital fibroblasts. STAT3 mRNA expression was higher in GO orbital tissues than in non-GO tissues. Treatment with proinflammatory cytokines, thyroid-stimulating hormone, or insulin-like growth factor-1 induced STAT3 mRNA in GO orbital fibroblasts, but not in non-GO cells. STAT3 silencing inhibited interleukin-1β-induced inflammatory cytokines and oxidative stress-induced haem oxygenase-1 expression. STAT3 siRNA-transfected GO orbital fibroblasts showed decreased adipocyte differentiation. STAT3 affected proinflammatory cytokine production, oxidative stress responses, and adipogenesis in an in vitro model of GO, suggesting that STAT3 mediates GO pathology, and that modulating STAT3 expression may have therapeutic potential against GO.

Original languageEnglish
Article number111363
JournalMolecular and Cellular Endocrinology
Volume534
DOIs
Publication statusPublished - 2021 Aug 20

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 ]. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2021 Elsevier B.V.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Fingerprint

Dive into the research topics of 'Signal transducer and activator of transcription 3 as a potential therapeutic target for Graves’ orbitopathy'. Together they form a unique fingerprint.

Cite this