CD34+ Orbital Fibroblasts Contribute to the Pathogenesis of Thyroid Eye Disease via miR-182-5p

Baiguang Yu1,2,3,4, Yi Wang1,2,3,4, Jun Jin1,2,3,4

  • 1Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, and Center for Basic Medical Research and Innovation in Visual System Diseases of Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.

Abstract

Insights

MicroRNA-182-5p (miR-182-5p) promotes thyroid eye disease (TED) by activating CD34+ orbital fibroblasts. Targeting miR-182-5p and its downstream effects on Smad7 offers a potential therapeutic strategy for TED.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Immunology

Background:

  • CD34+ orbital fibroblasts (OFs) are implicated in the pathogenesis of thyroid eye disease (TED).
  • Specific microRNAs (miRNAs) are known to exacerbate TED progression.

Purpose of the Study:

  • To investigate the regulatory role of miRNAs in CD34+ OFs.
  • To identify potential therapeutic targets for TED.

Main Methods:

  • A case-control study involving orbital connective tissues (OCTs) and OFs from TED patients and healthy donors.
  • MiRNA sequencing (miRNA-seq) to identify differentially expressed miRNAs, focusing on miR-182-5p.
  • Analysis of upstream regulators, downstream targets, and functional impact of miR-182-5p in CD34+ OFs.

Main Results:

  • miR-182-5p was significantly upregulated in TED OCTs and CD34+ OFs.
  • The IL-6/STAT3 signaling pathway was found to promote miR-182-5p expression in CD34+ OFs.
  • miR-182-5p enhanced CD34+ OF proliferation, migration, and fibrosis while inhibiting apoptosis, partly through targeting Smad7.

Conclusions:

  • The IL-6/STAT3/miR-182-5p pathway activates CD34+ OFs in TED.
  • miR-182-5p promotes key pathogenic features of CD34+ OFs by targeting Smad7.
  • miR-182-5p represents a promising therapeutic target for thyroid eye disease.

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