{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T10:20:55Z","timestamp":1793960455867,"version":"4.8.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Graves\u2019 orbitopathy (GO) is characterized by increased production of proinflammatory cytokines and hyaluronic acid by fibroblasts and their differentiation into adipocytes in response to immunologic stimuli. The suppressor of cytokine signaling-3 (\n                      <jats:italic>SOCS3<\/jats:italic>\n                      ) is an inducible negative regulator of the JAK\/STAT pathway, implicated in various inflammatory diseases. In this study, we investigated the role of SOCS3 in the inflammatory and adipogenic pathogenesis of GO.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Transcriptome profiling of orbital tissues obtained from five patients with GO who underwent orbital decompression surgery and four healthy subjects was performed using RNA-sequencing. Among the top-ranked differentially expressed genes, we identified 24 hub genes and found\n                      <jats:italic>SOCS3<\/jats:italic>\n                      to be the most significantly upregulated gene in GO samples compared with that in healthy tissue based on quantitative real-time polymerase chain reaction.\n                      <jats:italic>SOCS3<\/jats:italic>\n                      expression was analyzed in IL-1\u03b2-, and IGF-1-stimulated orbital fibroblasts using quantitative real-time polymerase chain reaction and western blot analysis. Knockdown of SOCS3 using siRNA transfection was performed to assess the effect of SOCS3 on the production of proinflammatory cytokines and adipogenic phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 184 consistently differentially expressed genes\u2014120 upregulated and 64 downregulated\u2014 in GO tissues compared to the control.\n                      <jats:italic>SOCS3<\/jats:italic>\n                      mRNA expression was significantly higher in GO tissues (\n                      <jats:italic>n<\/jats:italic>\n                      = 17) compared with that in control (\n                      <jats:italic>n<\/jats:italic>\n                      = 15). IL-1\u03b2 and IGF-1 enhanced the expression of\n                      <jats:italic>SOCS3<\/jats:italic>\n                      at mRNA and protein levels. Silencing of SOCS3 suppressed the levels of IL-1\u03b2-induced proinflammatory cytokines, including IL-6, IL-8, and ICAM-1. Phosphorylation of NF-kB and Akt was suppressed and adipogenic differentiation was significantly attenuated by SOCS3 knockdown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>SOCS3<\/jats:italic>\n                      was remarkably expressed in the adipose tissues of patients with GO and was induced by IL-1\u03b2 and IGF-1 in orbital fibroblasts. SOCS3 inhibition attenuated the production of proinflammatory cytokines and adipogenesis, suggesting that\n                      <jats:italic>SOCS3<\/jats:italic>\n                      may be a therapeutic target for controlling the inflammatory and adipogenic mechanisms in GO.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1527275","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:21:25Z","timestamp":1741047685000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Role of the suppressor of cytokine signaling-3 in the pathogenesis of Graves\u2019 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