{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:00:35Z","timestamp":1791928835412,"version":"4.3.4"},"reference-count":51,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"13","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2024,11,6]]},"DOI":"10.1167\/iovs.65.13.13","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T11:31:00Z","timestamp":1730892660000},"page":"13","source":"Crossref","is-referenced-by-count":6,"title":["Characteristics of Hyaluronan Metabolism During Myofibroblast Differentiation in Orbital Fibroblasts"],"prefix":"10.1167","volume":"65","author":[{"given":"Fruzsina R.","family":"Papp","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary"},{"name":"Doctoral School of Health Sciences, University of Debrecen, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Katko","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Csiki","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary"},{"name":"Doctoral School of Health Sciences, University of Debrecen, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Galgoczi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsanett","family":"Molnar","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Erdei","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miklos","family":"Bodor","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zita","family":"Steiber","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadett","family":"Ujhelyi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Endre V.","family":"Nagy","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"issue":"11","key":"bib1","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/s41574-024-01016-5","article-title":"Graves disease: latest understanding of pathogenesis and treatment options","volume":"20","author":"Lanzolla","year":"2024","journal-title":"Nat Rev Endocrinol"},{"issue":"6","key":"bib2","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/BF03347732","article-title":"TSH receptor gene expression in retroocular fibroblasts","volume":"17","author":"Mengistu","year":"1994","journal-title":"J Endocrinol Invest"},{"issue":"suppl 1","key":"bib3","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1210\/clinem\/dgac045","article-title":"It takes two to tango: IGF-I and TSH receptors in thyroid eye disease","volume":"107","author":"Girnita","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"bib4","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1111\/joim.13524","article-title":"Current concepts regarding Graves\u2019 orbitopathy","volume":"292","author":"Bartalena","year":"2022","journal-title":"J Intern Med"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"1392956","DOI":"10.3389\/fimmu.2024.1392956","article-title":"Immune checkpoints: new insights into the pathogenesis of thyroid eye disease","volume":"15","author":"Shu","year":"2024","journal-title":"Front Immunol"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"5391","DOI":"10.2147\/OTT.S336548","article-title":"M2-type macrophages induce Tregs generation by activating the TGF-\u00df\/Smad signalling pathway to promote colorectal cancer development","volume":"14","author":"Ma","year":"2021","journal-title":"Onco Targets Ther"},{"issue":"1","key":"bib7","doi-asserted-by":"publisher","first-page":"9622","DOI":"10.1038\/s41598-019-46075-1","article-title":"Macrophages promote a profibrotic phenotype in orbital fibroblasts through increased hyaluronic acid production and cell contractility","volume":"9","author":"Yang","year":"2019","journal-title":"Sci Rep"},{"issue":"11","key":"bib8","doi-asserted-by":"publisher","first-page":"3913","DOI":"10.1167\/iovs.05-0605","article-title":"Autologous T-lymphocytes stimulate proliferation of orbital fibroblasts derived from patients with Graves\u2019 ophthalmopathy","volume":"46","author":"Feldon","year":"2005","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"3","key":"bib9","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/j.survophthal.2021.08.010","article-title":"Thinking inside the box: current insights into targeting orbital tissue remodeling and inflammation in thyroid eye disease","volume":"67","author":"Gupta","year":"2022","journal-title":"Surv Ophthalmol"},{"issue":"6","key":"bib10","doi-asserted-by":"publisher","first-page":"2952","DOI":"10.3390\/ijms22062952","article-title":"JNK and p38 inhibitors prevent transforming growth factor-\u00df1-induced myofibroblast transdifferentiation in human Graves\u2019 orbital fibroblasts","volume":"22","author":"Hou","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"11","key":"bib11","doi-asserted-by":"publisher","first-page":"e0256812","DOI":"10.1371\/journal.pone.0256812","article-title":"Myofibroblast transdifferentiation is associated with changes in cellular and extracellular vesicle miRNA abundance","volume":"16","author":"Zainal Abidin","year":"2021","journal-title":"PLoS One"},{"issue":"6","key":"bib12","doi-asserted-by":"publisher","first-page":"735","DOI":"10.4142\/jvs.2018.19.6.735","article-title":"TGF-\u00df1 upregulates the expression of hyaluronan synthase 2 and hyaluronan synthesis in culture models of equine articular chondrocytes","volume":"19","author":"Ongchai","year":"2018","journal-title":"J Vet Sci"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"109392","DOI":"10.1016\/j.cellsig.2019.109392","article-title":"TGF-\u00df1 promotes hyaluronan synthesis by upregulating hyaluronan synthase 2 expression in human granulosa-lutein cells","volume":"63","author":"Wang","year":"2019","journal-title":"Cell Signal"},{"issue":"4-5","key":"bib14","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1080\/03008200490523031","article-title":"Differential stimulation of three forms of hyaluronan synthase by TGF-\u00df, IL-1\u00df, and TNF-a","volume":"45","author":"Oguchi","year":"2004","journal-title":"Connect Tissue Res"},{"issue":"11","key":"bib15","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.3390\/biom10111525","article-title":"Hyaluronan: metabolism and function","volume":"10","author":"Kobayashi","year":"2020","journal-title":"Biomolecules"},{"issue":"52","key":"bib16","doi-asserted-by":"publisher","first-page":"30910","DOI":"10.1074\/jbc.M115.673566","article-title":"Regulation of hyaluronan (HA) metabolism mediated by HYBID (hyaluronan-binding protein involved in HA depolymerization, KIAA1199) and HA synthases in growth factor-stimulated fibroblasts","volume":"290","author":"Nagaoka","year":"2015","journal-title":"J Biol Chem"},{"issue":"6","key":"bib17","doi-asserted-by":"publisher","first-page":"2108","DOI":"10.1096\/fj.201500178R","article-title":"Respective roles of hyaluronidases 1 and 2 in endogenous hyaluronan turnover","volume":"30","author":"Bourguignon","year":"2016","journal-title":"FASEB J"},{"issue":"1","key":"bib18","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.bbrc.2018.09.097","article-title":"The role and regulation of TMEM2 (transmembrane protein 2) in HYBID (hyaluronan (HA)-binding protein involved in HA depolymerization\/KIAA1199\/CEMIP)-mediated HA depolymerization in human skin fibroblasts","volume":"505","author":"Yoshino","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"issue":"6","key":"bib19","doi-asserted-by":"publisher","first-page":"104826","DOI":"10.1016\/j.jbc.2023.104826","article-title":"Human TMEM2 is not a catalytic hyaluronidase, but a regulator of hyaluronan metabolism via HYBID (KIAA1199\/CEMIP) and HAS2 expression","volume":"299","author":"Sato","year":"2023","journal-title":"J Biol Chem"},{"issue":"5","key":"bib20","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.tem.2022.02.002","article-title":"The membrane receptor CD44: novel insights into metabolism","volume":"33","author":"Weng","year":"2022","journal-title":"Trends Endocrinol Metab"},{"issue":"2","key":"bib21","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1002\/jcb.20405","article-title":"TGF-\u00df induced hyaluronan synthesis in orbital fibroblasts involves protein kinase C \u00dfII activation in vitro","volume":"95","author":"Wang","year":"2005","journal-title":"J Cell Biochem"},{"issue":"8","key":"bib22","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1056\/NEJMra0905750","article-title":"Graves\u2019 ophthalmopathy","volume":"362","author":"Bahn","year":"2010","journal-title":"N Engl J Med"},{"issue":"1","key":"bib23","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1136\/bjophthalmol-2015-307399","article-title":"Pathogenesis of thyroid eye disease: review and update on molecular mechanisms","volume":"100","author":"Khong","year":"2016","journal-title":"Br J Ophthalmol"},{"issue":"4","key":"bib24","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1210\/jcem-65-4-665","article-title":"Human retroocular fibroblasts in vitro: a model for the study of Graves\u2019 ophthalmopathy","volume":"65","author":"Bahn","year":"1987","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"bib25","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.yexcr.2013.09.021","article-title":"Hyaluronan synthase 1 (HAS1) produces a cytokine-and glucose-inducible, CD44-dependent cell surface coat","volume":"320","author":"Siiskonen","year":"2014","journal-title":"Exp Cell Res"},{"issue":"2","key":"bib26","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1530\/JOE-15-0524","article-title":"Cell density-dependent stimulation of PAI-1 and hyaluronan synthesis by TGF-\u00df in orbital fibroblasts","volume":"229","author":"Galgoczi","year":"2016","journal-title":"J Endocrinol"},{"issue":"8","key":"bib27","doi-asserted-by":"publisher","first-page":"5299","DOI":"10.1074\/jbc.M807965200","article-title":"Primary murine airway smooth muscle cells exposed to poly(I,C) or tunicamycin synthesize a leukocyte-adhesive hyaluronan matrix","volume":"284","author":"Lauer","year":"2009","journal-title":"J Biol Chem"},{"issue":"1","key":"bib28","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.ab.2011.05.023","article-title":"Improved agarose gel electrophoresis method and molecular mass calculation for high molecular mass hyaluronan","volume":"417","author":"Cowman","year":"2011","journal-title":"Anal Biochem"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/978-1-4939-9133-4","article-title":"Methods for hyaluronan molecular mass determination by agarose gel electrophoresis","volume":"1952","author":"Cowman","year":"2019","journal-title":"Methods Mol Biol"},{"issue":"2","key":"bib30","doi-asserted-by":"publisher","first-page":"101620","DOI":"10.1016\/j.beem.2022.101620","article-title":"Pathophysiology of thyroid-associated orbitopathy","volume":"37","author":"Lee","year":"2022","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"3","key":"bib31","doi-asserted-by":"publisher","first-page":"C672","DOI":"10.1152\/ajpcell.00451.2009","article-title":"Novel anti-adipogenic activity produced by human fibroblasts","volume":"299","author":"Lehmann","year":"2010","journal-title":"Am J Physiol Cell Physiol"},{"issue":"4","key":"bib32","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1016\/S0002-9440(10)63488-8","article-title":"Thy-1 expression in human fibroblast subsets defines myofibroblastic or lipofibroblastic phenotypes","volume":"163","author":"Koumas","year":"2003","journal-title":"Am J Pathol"},{"issue":"3","key":"bib33","doi-asserted-by":"publisher","first-page":"e20190103","DOI":"10.1084\/jem.20190103","article-title":"Transforming growth factor-\u00df in tissue fibrosis","volume":"217","author":"Frangogiannis","year":"2020","journal-title":"J Exp Med"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"412158","DOI":"10.1155\/2014\/412158","article-title":"Markers of inflammation and fibrosis in the orbital fat\/connective tissue of patients with Graves\u2019 orbitopathy: clinical implications","volume":"2014","author":"Pawlowski","year":"2014","journal-title":"Mediators Inflamm"},{"issue":"12","key":"bib35","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1089\/thy.2023.0309","article-title":"Yes-associated protein mediates the transition from inflammation to fibrosis in Graves\u2019 orbitopathy","volume":"33","author":"Ko","year":"2023","journal-title":"Thyroid"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"891922","DOI":"10.3389\/fendo.2022.891922","article-title":"Dihydroartemisinin exerts antifibrotic and anti-inflammatory effects in Graves\u2019 ophthalmopathy by targeting orbital fibroblasts","volume":"13","author":"Yang","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"10","key":"bib37","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1167\/iovs.63.10.6","article-title":"Potential therapeutic activity of berberine in thyroid-associated ophthalmopathy: inhibitory effects on tissue remodeling in orbital fibroblasts","volume":"63","author":"Diao","year":"2022","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"6","key":"bib38","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/j.stemcr.2015.05.004","article-title":"Expression of a-smooth muscle actin determines the fate of mesenchymal stromal cells","volume":"4","author":"Talele","year":"2015","journal-title":"Stem Cell Reports"},{"issue":"8","key":"bib39","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1038\/s41580-024-00716-0","article-title":"Fibroblast and myofibroblast activation in normal tissue repair and fibrosis","volume":"25","author":"Younesi","year":"2024","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"4","key":"bib40","doi-asserted-by":"publisher","first-page":"221","DOI":"10.3109\/08916939808993834","article-title":"T cell interactions with extracellular matrix proteins in patients with thyroid-associated ophthalmopathy","volume":"27","author":"Bednarczuk","year":"1998","journal-title":"Autoimmunity"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1146\/annurev-cellbio-100109-104020","article-title":"Assembly of fibronectin extracellular matrix","volume":"26","author":"Singh","year":"2010","journal-title":"Annu Rev Cell Dev Biol"},{"issue":"12","key":"bib42","doi-asserted-by":"publisher","first-page":"3189","DOI":"10.1016\/j.ajpath.2016.08.017","article-title":"The aryl hydrocarbon receptor and its ligands inhibit myofibroblast formation and activation: implications for thyroid eye disease","volume":"186","author":"Woeller","year":"2016","journal-title":"Am J Pathol"},{"issue":"4","key":"bib43","doi-asserted-by":"publisher","first-page":"a022145","DOI":"10.1101\/cshperspect.a022145","article-title":"TGF-\u00df family signaling in the control of cell proliferation and survival","volume":"9","author":"Zhang","year":"2017","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"10","key":"bib44","doi-asserted-by":"publisher","first-page":"6530","DOI":"10.1074\/jbc.M704819200","article-title":"Hyaluronan facilitates transforming growth factor-\u00df1-mediated fibroblast proliferation","volume":"283","author":"Meran","year":"2008","journal-title":"J Biol Chem"},{"issue":"5","key":"bib45","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1007\/s11224-008-9370-3","article-title":"Molecular structure of hyaluronan: an introduction","volume":"19","author":"Hargittai","year":"2008","journal-title":"Struct Chem"},{"issue":"2","key":"bib46","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1167\/iovs.61.2.27","article-title":"Characteristics of hyaluronan synthesis inhibition by 4-methylumbelliferone in orbital fibroblasts","volume":"61","author":"Galgoczi","year":"2020","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"40","key":"bib47","doi-asserted-by":"publisher","first-page":"41453","DOI":"10.1074\/jbc.M401678200","article-title":"Myofibroblastic differentiation leads to hyaluronan accumulation through reduced hyaluronan turnover","volume":"279","author":"Jenkins","year":"2004","journal-title":"J Biol Chem"},{"issue":"2","key":"bib48","doi-asserted-by":"publisher","first-page":"105607","DOI":"10.1016\/j.jbc.2023.105607","article-title":"TMEM2 inhibits the development of Graves\u2019 orbitopathy through the JAK-STAT signaling pathway","volume":"300","author":"Li","year":"2024","journal-title":"J Biol Chem"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"2787","DOI":"10.3389\/fimmu.2018.02787","article-title":"Hyaluronan and its interactions with immune cells in the healthy and inflamed lung","volume":"9","author":"Johnson","year":"2018","journal-title":"Front Immunol"},{"issue":"35","key":"bib50","doi-asserted-by":"publisher","first-page":"25085","DOI":"10.1074\/jbc.274.35.25085","article-title":"Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties","volume":"274","author":"Itano","year":"1999","journal-title":"J Biol Chem"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"790203","DOI":"10.1155\/2015\/790203","article-title":"Hyaluronan's role in fibrosis: a pathogenic factor or a passive player?","volume":"2015","author":"Albeiroti","year":"2015","journal-title":"Biomed Res Int"}],"container-title":["Investigative Ophthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2802208","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:47Z","timestamp":1791927107000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2802208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,6]]},"references-count":51,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2024,11,4]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.65.13.13","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2024,11,6]]}}}