{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:35:12Z","timestamp":1784028912704,"version":"3.55.0"},"reference-count":34,"publisher":"Korean Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1C1C1006434"],"award-info":[{"award-number":["2022R1C1C1006434"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["e-enm.org"],"crossmark-restriction":true},"short-container-title":["Endocrinol Metab"],"published-print":{"date-parts":[[2024,10,31]]},"abstract":"<jats:p>Background: Thyroid-associated ophthalmopathy (TAO) involves tissue expansion and inflammation, potentially causing a hypoxic microenvironment. Hypoxia-inducible factor (HIF)-1\u03b1 is crucial in fibrosis and adipogenesis, which are observed in TAO progression. We investigated the effects of hypoxia on orbital fibroblasts (OFs) in TAO, focusing on the role of HIF-1\u03b1 in TAO progression.Methods: OFs were isolated from TAO and non-TAO patients (as controls). In addition to HIF-1\u03b1, adipogenic differentiation markers including peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) and CCAAT\/enhancer binding protein (CEBP) were measured by Western blot, and phenotype changes were evaluated by Oil Red O staining under both normoxia and hypoxia. To elucidate the effect of HIF-1\u03b1 inhibition, protein expression changes after HIF-1\u03b1 inhibitor treatment were evaluated under normoxia and hypoxia.Results: TAO OFs exhibited significantly higher HIF-1\u03b1 expression than non-TAO OFs, and the difference was more distinct under hypoxia than under normoxia. Oil Red O staining showed that adipogenic differentiation of TAO OFs was prominent under hypoxia. Hypoxic conditions increased the expression of adipogenic markers, namely PPAR\u03b3 and CEBP, as well as HIF-1\u03b1 in TAO OFs. Interleukin 6 levels also increased in response to hypoxia. The effect of hypoxia on adipogenesis was reduced at the protein level after HIF-1\u03b1 inhibitor treatment, and this inhibitory effect was sustained even with IGF-1 stimulation in addition to hypoxia.Conclusion: Hypoxia induces tissue remodeling in TAO by stimulating adipogenesis through HIF-1\u03b1 activation. These data could provide insights into new treatment strategies and the mechanisms of adipose tissue remodeling in TAO.<\/jats:p>","DOI":"10.3803\/enm.2024.1952","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T07:34:00Z","timestamp":1729064040000},"page":"767-776","update-policy":"https:\/\/doi.org\/10.3803\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["In Vitro Investigation of HIF-1\u03b1 as a Therapeutic Target for Thyroid-Associated 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