PMID- 33498689 OWN - NLM STAT- MEDLINE DCOM- 20210903 LR - 20210903 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 3 DP - 2021 Jan 23 TI - Tear-Derived Exosome Proteins Are Increased in Patients with Thyroid Eye Disease. LID - 10.3390/ijms22031115 [doi] LID - 1115 AB - Exosomes contain proteins, lipids, RNA, and DNA that mediate intercellular signaling. Exosomes can contribute to the pathological processes of various diseases, although their roles in ocular diseases are unclear. We aimed to isolate exosomes from tear fluids (TF) of patients with Thyroid eye disease (TED) and analyze the exosomal proteins. TFs were collected from eight patients with TED and eight control subjects. The number of TF exosomes were measured using nanoparticle-tracking analysis. The expression of specific proteins in the purified exosome pellets were analyzed using a Proteome Profiler Array Kit. Cultured normal orbital fibroblasts were incubated with TF exosomes from patients with TED and control subjects, and changes in inflammatory cytokine levels were compared. TF exosomes from TED patients showed more exosomes than the control subjects. The expression levels of exosomal proteins vitamin D-binding (VDB) protein, C-reactive protein (CRP), chitinase 3-like 1 (CHI3L1), matrix metalloproteinase-9 (MMP-9), and vascular adhesion molecule-1 (VCAM-1) were significantly increased in patients with TED, compared to those of controls. Orbital fibroblasts exposed to TF exosomes from patients with TED showed significantly higher levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) production than those treated with control TF exosomes. Specific proteins showed higher expression in exosomes from TED patients, implying that they may play keys roles in TED pathogenesis. FAU - Han, Jeong-Sun AU - Han JS AUID- ORCID: 0000-0002-4491-626X AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. FAU - Kim, Sung Eun AU - Kim SE AD - Department of Ophthalmology and Visual Science, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. FAU - Jin, Jun-Qing AU - Jin JQ AUID- ORCID: 0000-0002-5018-7008 AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. FAU - Park, Na Ri AU - Park NR AD - Department of Ophthalmology and Visual Science, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. FAU - Lee, Ji-Young AU - Lee JY AD - Department of Pathology, Institute of Hansen's Disease, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. FAU - Kim, Hong Lim AU - Kim HL AD - Integrative Research Support Center, Laboratory of Electron Microscope, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. FAU - Lee, Seong-Beom AU - Lee SB AD - Department of Pathology, Institute of Hansen's Disease, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. FAU - Yang, Suk-Woo AU - Yang SW AD - Department of Ophthalmology and Visual Science, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. FAU - Lim, Dong-Jun AU - Lim DJ AUID- ORCID: 0000-0003-0995-6482 AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. LA - eng GR - 2019R1I1A1A01059472/the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education/ PT - Journal Article DEP - 20210123 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (CHI3L1 protein, human) RN - 0 (Chitinase-3-Like Protein 1) RN - 0 (Cytokines) RN - 0 (Eye Proteins) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 0 (Vitamin D-Binding Protein) RN - 0 (tear proteins) RN - 554Z48XN5E (Methimazole) RN - EC 3.4.24.35 (MMP9 protein, human) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Adult MH - Aged MH - Case-Control Studies MH - Chitinase-3-Like Protein 1/analysis/metabolism MH - Cytokines/analysis/metabolism MH - Exosomes/*chemistry/pathology MH - Eye Proteins/analysis/*metabolism MH - Female MH - Fibroblasts/metabolism MH - Graves Ophthalmopathy/drug therapy/*pathology MH - Humans MH - Male MH - Matrix Metalloproteinase 9/analysis/metabolism MH - Methimazole/therapeutic use MH - Middle Aged MH - Tears/*cytology/metabolism MH - Vascular Cell Adhesion Molecule-1/analysis/metabolism MH - Vitamin D-Binding Protein/analysis/metabolism PMC - PMC7866068 OTO - NOTNLM OT - Graves' ophthalmopathy OT - eear fluids OT - ehyroid-associated ophthalmopathy OT - exosomes OT - extracellular vesicle OT - eytokines COIS- The authors declare no conflict of interest. EDAT- 2021/01/28 06:00 MHDA- 2021/09/04 06:00 PMCR- 2021/01/23 CRDT- 2021/01/27 01:07 PHST- 2020/12/23 00:00 [received] PHST- 2021/01/14 00:00 [revised] PHST- 2021/01/20 00:00 [accepted] PHST- 2021/01/27 01:07 [entrez] PHST- 2021/01/28 06:00 [pubmed] PHST- 2021/09/04 06:00 [medline] PHST- 2021/01/23 00:00 [pmc-release] AID - ijms22031115 [pii] AID - ijms-22-01115 [pii] AID - 10.3390/ijms22031115 [doi] PST - epublish SO - Int J Mol Sci. 2021 Jan 23;22(3):1115. doi: 10.3390/ijms22031115.