Tear-derived exosomal biomarkers of Graves’ ophthalmopathy

Graves’ ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves’ disease (GD), can lead to a significant decline in the quality of life in patients. Exosomes, which contain proteins, lipids and DNA, play important roles in the pathological processes of various diseases. However...

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Main Authors: Ting-Ting Shi, Ru-Xuan Zhao, Zhong Xin, Zhi-Jia Hou, Hua Wang, Rong-Rong Xie, Dong-Mei Li, Jin-Kui Yang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-12-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.1088606/full
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author Ting-Ting Shi
Ru-Xuan Zhao
Zhong Xin
Zhi-Jia Hou
Hua Wang
Rong-Rong Xie
Dong-Mei Li
Jin-Kui Yang
author_facet Ting-Ting Shi
Ru-Xuan Zhao
Zhong Xin
Zhi-Jia Hou
Hua Wang
Rong-Rong Xie
Dong-Mei Li
Jin-Kui Yang
author_sort Ting-Ting Shi
collection DOAJ
description Graves’ ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves’ disease (GD), can lead to a significant decline in the quality of life in patients. Exosomes, which contain proteins, lipids and DNA, play important roles in the pathological processes of various diseases. However, their roles in Graves’ ophthalmopathy are still unclear. We aimed to isolate exosomes and analyze the different exosomal proteins. Tear fluids were collected from twenty-four GO patients, twenty-four GD patients and sixteen control subjects. The numbers of tear exosomes were assayed using nanoparticle tracking analysis. A Luminex 200 kit and ELISA kit were used to confirm the different cytokine concentrations in serum. Extraocular muscle from GO patients and controls was extracted, and western blotting was used to assay the levels of Caspase-3 and complement C4A. Our study demonstrated that the number of tear exosomes differ from GD patients and control. The expression levels of cytokines, including IL-1 and IL-18, were significantly increased in the tear exosomes and serum from GO patients compared with GD patients and controls. The levels of the exosomal proteins Caspase-3, complement C4A and APOA-IV were significantly increased in GO patients compared to GD patients and controls. Orbital fibroblasts from GO patients showed significantly higher levels of Caspase-3 and complement C4A than those from controls. The levels of serum APOA-IV in GO patients were significantly higher than those in GD patients and controls. Specific proteins showed elevated expression in tear exosomes from GO patients, indicating that they may play important roles in GO pathogenesis.
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spelling doaj.art-4aa33841f98645958bdb6838b8e810472022-12-22T02:49:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10886061088606Tear-derived exosomal biomarkers of Graves’ ophthalmopathyTing-Ting Shi0Ru-Xuan Zhao1Zhong Xin2Zhi-Jia Hou3Hua Wang4Rong-Rong Xie5Dong-Mei Li6Jin-Kui Yang7Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Diabetes Research and Care, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaDepartment of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaDepartment of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaDepartment of Emergency, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Diabetes Research and Care, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaDepartment of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Diabetes Research and Care, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaGraves’ ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves’ disease (GD), can lead to a significant decline in the quality of life in patients. Exosomes, which contain proteins, lipids and DNA, play important roles in the pathological processes of various diseases. However, their roles in Graves’ ophthalmopathy are still unclear. We aimed to isolate exosomes and analyze the different exosomal proteins. Tear fluids were collected from twenty-four GO patients, twenty-four GD patients and sixteen control subjects. The numbers of tear exosomes were assayed using nanoparticle tracking analysis. A Luminex 200 kit and ELISA kit were used to confirm the different cytokine concentrations in serum. Extraocular muscle from GO patients and controls was extracted, and western blotting was used to assay the levels of Caspase-3 and complement C4A. Our study demonstrated that the number of tear exosomes differ from GD patients and control. The expression levels of cytokines, including IL-1 and IL-18, were significantly increased in the tear exosomes and serum from GO patients compared with GD patients and controls. The levels of the exosomal proteins Caspase-3, complement C4A and APOA-IV were significantly increased in GO patients compared to GD patients and controls. Orbital fibroblasts from GO patients showed significantly higher levels of Caspase-3 and complement C4A than those from controls. The levels of serum APOA-IV in GO patients were significantly higher than those in GD patients and controls. Specific proteins showed elevated expression in tear exosomes from GO patients, indicating that they may play important roles in GO pathogenesis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1088606/fullGraves’ ophthalmopathybiomarkerexosometearCaspase-3APOA-IV
spellingShingle Ting-Ting Shi
Ru-Xuan Zhao
Zhong Xin
Zhi-Jia Hou
Hua Wang
Rong-Rong Xie
Dong-Mei Li
Jin-Kui Yang
Tear-derived exosomal biomarkers of Graves’ ophthalmopathy
Frontiers in Immunology
Graves’ ophthalmopathy
biomarker
exosome
tear
Caspase-3
APOA-IV
title Tear-derived exosomal biomarkers of Graves’ ophthalmopathy
title_full Tear-derived exosomal biomarkers of Graves’ ophthalmopathy
title_fullStr Tear-derived exosomal biomarkers of Graves’ ophthalmopathy
title_full_unstemmed Tear-derived exosomal biomarkers of Graves’ ophthalmopathy
title_short Tear-derived exosomal biomarkers of Graves’ ophthalmopathy
title_sort tear derived exosomal biomarkers of graves ophthalmopathy
topic Graves’ ophthalmopathy
biomarker
exosome
tear
Caspase-3
APOA-IV
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.1088606/full
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