TSG6 Plays a Role in Improving Orbital Inflammatory Infiltration and Extracellular Matrix Accumulation in TAO Model Mice

Abstract

Introduction

TSG-6 plays a wide anti-inflammatory and therapeutic role in a variety of autoimmune diseases as the key mediator of mesenchymal stem cells (MSCs).

Purpose

We aimed to test whether TSG-6 could exert similar effects as MSCS in TAO via establishing TAO animal model immunized by hTSHR-A subunit plasmid.

Material and Methods

We tested the expression level of TSG-6 on intraconal orbital fat from controls and patients with TAO. We established a stable thyroid-associated ophthalmopathy animal model by immunizing 6-week-old female Balb/c mice with recombination hTSHR-A subunit plasmid. After four immunizations, TSG-6 or dexamethasone was injected through the tail vein. The effects of the drugs on body weight, thyroid function, orbital inflammation, fibrosis and lipogenesis were observed.

Results

The expression of TSG-6 in the orbital tissues of TAO patient is lower than that of normal people. In our animal model, mice showed weight loss, higher TT4 and TSHR antibody levels, and ocular symptoms such as inflammation and proptosis. TSG-6 can reduce ocular fibrosis and lipogenesis by inhibiting the infiltration of CD3+ T lymphocytes and macrophages in the mouse model of thyroid associated ophthalmopathy. Compared with dexamethasone, TSG-6 showed comparable anti-inflammatory effect, moreover, it has given a better performance in inhibiting adipogenesis.

Conclusion

It was demonstrated that TSG-6 has a considerable positive impact on improving eye symptoms of TAO mice, which could be a novel candidate for the early treatment of TAO.

Keywords:

• TAO
• TSG-6
• hTSHR-A subunit plasmid
• anti-inflammatory
• anti-fibrosis
• lipogenesis

Ethics Approval and Informed Consent

This study was conducted with the approval of the Ethics Committee of the Second Affiliated Hospital of Anhui Medical University (approval number: YX2022-125), and written informed consent was obtained from all participants. All animal testing was in accordance with the guidelines set by the USA national institutes of health, and approved by the Anhui medical university animal ethics committee (approval number: LLSC20221257).

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This project was supported by the Clinical research training program of the Second Affiliated hospital of Anhui Medical University (2021LCZD11), Research Fund of Anhui Institute of Translational Medicine (2022zhyx-C73) and the Postgraduate Innovation Research and Practice Program of Anhui Medical University(approval number:YJS20230087).