{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:09:02Z","timestamp":1790028542375,"version":"4.0.1"},"reference-count":106,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:00:00Z","timestamp":1710374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007530","name":"Taiwan National Science and Technology Council","doi-asserted-by":"publisher","award":["112-2314-B-075-003-MY2"],"award-info":[{"award-number":["112-2314-B-075-003-MY2"]}],"id":[{"id":"10.13039\/501100007530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007530","name":"Taiwan National Science and Technology Council","doi-asserted-by":"publisher","award":["V113C-021"],"award-info":[{"award-number":["V113C-021"]}],"id":[{"id":"10.13039\/501100007530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital, Taiwan","doi-asserted-by":"publisher","award":["112-2314-B-075-003-MY2"],"award-info":[{"award-number":["112-2314-B-075-003-MY2"]}],"id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital, Taiwan","doi-asserted-by":"publisher","award":["V113C-021"],"award-info":[{"award-number":["V113C-021"]}],"id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Graves\u2019 ophthalmopathy (GO), or thyroid eye disease (TED), is the most frequent extrathyroidal manifestation of Graves\u2019 disease (GD). Inflammation and subsequent aberrant tissue remodeling with fibrosis are important pathogenesis. There are many proposed mechanisms and molecular pathways contributing to tissue remodeling and fibrosis in GO, including adipogenesis, fibroblast proliferation and myofibroblasts differentiation, oxidative stress, endoplasmic reticulum (ER) stress, hyaluronan (HA) and glycosaminoglycans (GAGs) accumulation in the extracellular matrix (ECM) and new concepts of epigenetics modification, such as histone modification, DNA methylation, non-coding RNAs, and gut microbiome. This review summarizes the current understanding of ECM proteins and associated tissue remodeling in the pathogenesis and potential mediators for the treatment of GO.<\/jats:p>","DOI":"10.3390\/ijms25063288","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T05:43:08Z","timestamp":1710394988000},"page":"3288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The Role of Fibrogenesis and Extracellular Matrix Proteins in the Pathogenesis of Graves\u2019 Ophthalmopathy"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8425-8823","authenticated-orcid":false,"given":"Hsun-I","family":"Chiu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 112, Taiwan"},{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3713-4710","authenticated-orcid":false,"given":"Shi-Bei","family":"Wu","sequence":"additional","affiliation":[{"name":"Biomedical Commercialization Center, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4411-3387","authenticated-orcid":false,"given":"Chieh-Chih","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 112, Taiwan"},{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41574-019-0305-4","article-title":"New insights into the pathogenesis and nonsurgical management of Graves orbitopathy","volume":"16","author":"Taylor","year":"2020","journal-title":"Nat. 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