{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T01:25:21Z","timestamp":1794273921289,"version":"4.9.0"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of\u00a0Hunan Province","doi-asserted-by":"publisher","award":["2021JJ40859"],"award-info":[{"award-number":["2021JJ40859"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Eye Research"],"published-print":{"date-parts":[[2022,4]]},"DOI":"10.1016\/j.exer.2022.108971","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T03:18:33Z","timestamp":1643599113000},"page":"108971","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"special_numbering":"C","title":["Botox-A improve the thyroid-associated ophthalmopathy (TAO) orbital fibroblast activation through inhibiting the TGF-\u03b2\/Smad signaling"],"prefix":"10.1016","volume":"217","author":[{"given":"Xin","family":"Qi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ban","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiying","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyu","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boding","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3017-9895","authenticated-orcid":false,"given":"Wei","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.exer.2022.108971_bib1","first-page":"115","article-title":"Isolation and phenotypic characterization of lung fibroblasts","volume":"117","author":"Baglole","year":"2005","journal-title":"Methods Mol. Med."},{"issue":"8","key":"10.1016\/j.exer.2022.108971_bib2","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1056\/NEJMra0905750","article-title":"Graves' ophthalmopathy","volume":"362","author":"Bahn","year":"2010","journal-title":"N. Engl. J. Med."},{"issue":"9","key":"10.1016\/j.exer.2022.108971_bib3","first-page":"2668","article-title":"Human orbital fibroblasts in culture express ganglioside profiles distinct from those in dermal fibroblasts","volume":"80","author":"Berenson","year":"1995","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"1","key":"10.1016\/j.exer.2022.108971_bib4","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1111\/j.1755-3768.2008.01171.x","article-title":"Repeated peribulbar injections of triamcinolone acetonide: a successful and safe treatment for moderate to severe Graves' ophthalmopathy","volume":"87","author":"Bordaberry","year":"2009","journal-title":"Acta Ophthalmol."},{"issue":"19","key":"10.1016\/j.exer.2022.108971_bib5","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1056\/NEJM199411103311907","article-title":"Transforming growth factor beta in tissue fibrosis","volume":"331","author":"Border","year":"1994","journal-title":"N. Engl. J. Med."},{"issue":"3","key":"10.1016\/j.exer.2022.108971_bib6","doi-asserted-by":"crossref","first-page":"451e","DOI":"10.1097\/PRS.0000000000004145","article-title":"Comparison of steroid and botulinum toxin type A monotherapy with combination therapy for treating human hypertrophic scars in an animal model","volume":"141","author":"Chen","year":"2018","journal-title":"Plast. Reconstr. Surg."},{"issue":"4","key":"10.1016\/j.exer.2022.108971_bib7","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/eye.2008.165","article-title":"Comparative study of Botox injection treatment for upper eyelid retraction with 6-month follow-up in patients with thyroid eye disease in the congestive or fibrotic stage","volume":"23","author":"Costa","year":"2009","journal-title":"Eye (Lond)"},{"issue":"8","key":"10.1016\/j.exer.2022.108971_bib8","doi-asserted-by":"crossref","first-page":"13342","DOI":"10.1002\/jcp.28011","article-title":"The Smad2\/3\/4 complex binds miR-139 promoter to modulate TGFbeta-induced proliferation and activation of human Tenon's capsule fibroblasts through the Wnt pathway","volume":"234","author":"Deng","year":"2019","journal-title":"J. Cell. Physiol."},{"issue":"1","key":"10.1016\/j.exer.2022.108971_bib9","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1210\/jc.2009-1614","article-title":"Increased generation of fibrocytes in thyroid-associated ophthalmopathy","volume":"95","author":"Douglas","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"11","key":"10.1016\/j.exer.2022.108971_bib10","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1136\/bjo.2004.046193","article-title":"Treatment of thyroid associated ophthalmopathy with periocular injections of triamcinolone","volume":"88","author":"Ebner","year":"2004","journal-title":"Br. J. Ophthalmol."},{"issue":"11","key":"10.1016\/j.exer.2022.108971_bib11","doi-asserted-by":"crossref","first-page":"3913","DOI":"10.1167\/iovs.05-0605","article-title":"Autologous T-lymphocytes stimulate proliferation of orbital fibroblasts derived from patients with Graves' ophthalmopathy","volume":"46","author":"Feldon","year":"2005","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"1","key":"10.1016\/j.exer.2022.108971_bib12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0925-4439(93)90085-F","article-title":"Pleotrophic action of interferon gamma in human orbital fibroblasts","volume":"1181","author":"Higgins","year":"1993","journal-title":"Biochim. Biophys. Acta"},{"issue":"2 Pt 1","key":"10.1016\/j.exer.2022.108971_bib13","doi-asserted-by":"crossref","first-page":"C359","DOI":"10.1152\/ajpcell.1995.269.2.C359","article-title":"Leukoregulin induces plasminogen activator inhibitor type 1 in human orbital fibroblasts","volume":"269","author":"Hogg","year":"1995","journal-title":"Am. J. Physiol."},{"issue":"2","key":"10.1016\/j.exer.2022.108971_bib14","doi-asserted-by":"crossref","first-page":"171e","DOI":"10.1097\/PRS.0000000000001438","article-title":"Effect of botulinum toxin type A on differentiation of fibroblasts derived from scar tissue","volume":"136","author":"Jeong","year":"2015","journal-title":"Plast. Reconstr. Surg."},{"issue":"6","key":"10.1016\/j.exer.2022.108971_bib16","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1167\/iovs.09-4257","article-title":"Antifibrotic effect of Pirfenidone on orbital fibroblasts of patients with thyroid-associated ophthalmopathy by decreasing TIMP-1 and collagen levels","volume":"51","author":"Kim","year":"2010","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"5","key":"10.1016\/j.exer.2022.108971_bib17","doi-asserted-by":"crossref","first-page":"821e","DOI":"10.1097\/PRS.0000000000002625","article-title":"Effect of botulinum toxin type A on TGF-beta\/smad pathway signaling: implications for silicone-induced capsule formation","volume":"138","author":"Kim","year":"2016","journal-title":"Plast. Reconstr. Surg."},{"issue":"7","key":"10.1016\/j.exer.2022.108971_bib18","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1096\/fj.03-1273rev","article-title":"TGF-beta signaling and the fibrotic response","volume":"18","author":"Leask","year":"2004","journal-title":"Faseb. J."},{"key":"10.1016\/j.exer.2022.108971_bib19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yexmp.2018.11.004","article-title":"Molecular biomarkers of Graves' ophthalmopathy","volume":"106","author":"Longo","year":"2019","journal-title":"Exp. Mol. Pathol."},{"issue":"5","key":"10.1016\/j.exer.2022.108971_bib20","first-page":"1018","article-title":"Detection and modulation of interleukin-1 receptor antagonist messenger ribonucleic acid and immunoreactivity in Graves' orbital fibroblasts","volume":"38","author":"Muhlberg","year":"1997","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"2","key":"10.1016\/j.exer.2022.108971_bib21","first-page":"CD006499","article-title":"Botulinum toxin for the treatment of strabismus","author":"Rowe","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.exer.2022.108971_bib22","first-page":"CD006499","article-title":"Botulinum toxin for the treatment of strabismus","volume":"3","author":"Rowe","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"issue":"2","key":"10.1016\/j.exer.2022.108971_bib23","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3109\/01676830903324268","article-title":"Transcutaneous dysport injection for treatment of upper eyelid retraction associated with thyroid eye disease","volume":"29","author":"Salour","year":"2010","journal-title":"Orbit"},{"issue":"3","key":"10.1016\/j.exer.2022.108971_bib24","doi-asserted-by":"crossref","first-page":"C707","DOI":"10.1152\/ajpcell.1998.274.3.C707","article-title":"Human orbital fibroblasts are activated through CD40 to induce proinflammatory cytokine production","volume":"274","author":"Sempowski","year":"1998","journal-title":"Am. J. Physiol."},{"issue":"3","key":"10.1016\/j.exer.2022.108971_bib26","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/0925-4439(93)90036-Z","article-title":"Bidimensional gel electrophoretic analysis of protein synthesis and response to interferon-gamma in cultured human dermal fibroblasts","volume":"1181","author":"Smith","year":"1993","journal-title":"Biochim. Biophys. Acta"},{"issue":"3","key":"10.1016\/j.exer.2022.108971_bib27","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/1523-1747.ep12469828","article-title":"Interferon gamma regulation of de novo protein synthesis in human dermal fibroblasts in culture is anatomic site dependent","volume":"100","author":"Smith","year":"1993","journal-title":"J. Invest. Dermatol."},{"issue":"1 Pt 1","key":"10.1016\/j.exer.2022.108971_bib28","doi-asserted-by":"crossref","first-page":"C24","DOI":"10.1152\/ajpcell.1992.263.1.C24","article-title":"Interferon-gamma is an inducer of plasminogen activator inhibitor type 1 in human orbital fibroblasts","volume":"263","author":"Smith","year":"1992","journal-title":"Am. J. Physiol."},{"issue":"1 Pt 1","key":"10.1016\/j.exer.2022.108971_bib29","doi-asserted-by":"crossref","first-page":"C138","DOI":"10.1152\/ajpcell.1993.265.1.C138","article-title":"Human orbital fibroblasts in culture bind and respond to endothelin","volume":"265","author":"Smith","year":"1993","journal-title":"Am. J. Physiol."},{"issue":"11","key":"10.1016\/j.exer.2022.108971_bib30","doi-asserted-by":"crossref","first-page":"5094","DOI":"10.1073\/pnas.91.11.5094","article-title":"Prostaglandin E2 elicits a morphological change in cultured orbital fibroblasts from patients with Graves ophthalmopathy","volume":"91","author":"Smith","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"9","key":"10.1016\/j.exer.2022.108971_bib31","first-page":"2620","article-title":"Evidence for cellular heterogeneity in primary cultures of human orbital fibroblasts","volume":"80","author":"Smith","year":"1995","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"12","key":"10.1016\/j.exer.2022.108971_bib32","doi-asserted-by":"crossref","first-page":"5576","DOI":"10.1210\/endo.138.12.5563","article-title":"Human thyroid fibroblasts exhibit a distinctive phenotype in culture: characteristic ganglioside profile and functional CD40 expression","volume":"138","author":"Smith","year":"1997","journal-title":"Endocrinology"},{"issue":"1","key":"10.1016\/j.exer.2022.108971_bib33","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1210\/jcem.87.1.8164","article-title":"Orbital fibroblast heterogeneity may determine the clinical presentation of thyroid-associated ophthalmopathy","volume":"87","author":"Smith","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"6","key":"10.1016\/j.exer.2022.108971_bib34","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1530\/eje.0.1360599","article-title":"Analysis of human thyrotropin receptor gene expression and immunoreactivity in human orbital tissue","volume":"136","author":"Spitzweg","year":"1997","journal-title":"Eur. J. Endocrinol."},{"issue":"3","key":"10.1016\/j.exer.2022.108971_bib35","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1046\/j.1365-2265.2003.01708.x","article-title":"TSH-R expression and cytokine profile in orbital tissue of active vs. inactive Graves' ophthalmopathy patients","volume":"58","author":"Wakelkamp","year":"2003","journal-title":"Clin. Endocrinol."},{"issue":"12","key":"10.1016\/j.exer.2022.108971_bib36","first-page":"3553","article-title":"Prostaglandin E2 alters human orbital fibroblast shape through a mechanism involving the generation of cyclic adenosine monophosphate","volume":"80","author":"Wang","year":"1995","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"1","key":"10.1016\/j.exer.2022.108971_bib37","first-page":"50","article-title":"[Effect of botulinum toxin type A on the expression of substance P, calcitonin gene-related peptide, transforming growth factor beta-1 and alpha smooth muscle actin A in wound healing in rats]","volume":"25","author":"Wang","year":"2009","journal-title":"Zhonghua Zhengxing Waike Zazhi"},{"issue":"4","key":"10.1016\/j.exer.2022.108971_bib38","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.3892\/mmr.2017.6277","article-title":"Role of hypoxiainducible factor1alpha in autophagic cell death in microglial cells induced by hypoxia","volume":"15","author":"Wang","year":"2017","journal-title":"Mol. Med. Rep."},{"issue":"11","key":"10.1016\/j.exer.2022.108971_bib39","doi-asserted-by":"crossref","first-page":"e0207354","DOI":"10.1371\/journal.pone.0207354","article-title":"Botulinum toxin A-induced muscle paralysis stimulates Hdac4 and differential miRNA expression","volume":"13","author":"Worton","year":"2018","journal-title":"PLoS One"},{"issue":"2","key":"10.1016\/j.exer.2022.108971_bib40","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/path.2277","article-title":"Cellular and molecular mechanisms of fibrosis","volume":"214","author":"Wynn","year":"2008","journal-title":"J. Pathol."},{"issue":"4","key":"10.1016\/j.exer.2022.108971_bib41","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1007\/s00266-009-9423-z","article-title":"Effect of botulinum toxin type A on transforming growth factor beta1 in fibroblasts derived from hypertrophic scar: a preliminary report","volume":"34","author":"Xiao","year":"2010","journal-title":"Aesthetic Plast. Surg."},{"issue":"8","key":"10.1016\/j.exer.2022.108971_bib42","first-page":"1290","article-title":"Long-term effect of triamcinolone acetonide in the treatment of upper lid retraction with thyroid associated ophthalmopathy","volume":"11","author":"Xu","year":"2018","journal-title":"Int. J. Ophthalmol."},{"issue":"15","key":"10.1016\/j.exer.2022.108971_bib43","doi-asserted-by":"crossref","first-page":"8904","DOI":"10.1073\/pnas.95.15.8904","article-title":"Leukoregulin induction of protein expression in human orbital fibroblasts: evidence for anatomical site-restricted cytokine-target cell interactions","volume":"95","author":"Young","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U. S. A."}],"container-title":["Experimental Eye Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483522000525?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483522000525?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T05:31:23Z","timestamp":1762147883000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014483522000525"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4]]},"references-count":41,"alternative-id":["S0014483522000525"],"URL":"https:\/\/doi.org\/10.1016\/j.exer.2022.108971","relation":{},"ISSN":["0014-4835"],"issn-type":[{"value":"0014-4835","type":"print"}],"subject":[],"published":{"date-parts":[[2022,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Botox-A improve the thyroid-associated ophthalmopathy (TAO) orbital fibroblast activation through inhibiting the TGF-\u03b2\/Smad signaling","name":"articletitle","label":"Article Title"},{"value":"Experimental Eye Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exer.2022.108971","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"108971"}}