{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:44:11Z","timestamp":1788921851008,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009253","name":"European Association for the Study of the Liver","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009253","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002924","name":"Federaci\u00f3n Espa\u00f1ola de Enfermedades Raras","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002924","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Progressive hepatic fibrosis can be considered the final stage of chronic liver disease. Hepatic stellate cells\u00a0(HSC) play a central role in liver fibrogenesis. Thyroid hormones (TH, e.g. thyroxine; T4 and triiodothyronine; T3) significantly affect development, growth, cell differentiation and metabolism through activation of TH receptor \u03b1 and\/or \u03b2 (TR\u03b1\/\u03b2). Here, we evaluated the influence of TH in hepatic fibrogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Human liver tissue was obtained from explanted livers following transplantation. TR\u03b1\u2010deficient (TR\u03b1\u2010KO) and wild\u2010type (WT) mice were fed a control or a profibrogenic methionine\u2010choline deficient (MCD) diet. Liver tissue was assessed by qRT\u2010PCR for fibrogenic gene expression. In vitro, HSC were treated with TGF\u03b2 in the presence or absence of T3. HSC with stable TR\u03b1 knockdown and TR\u03b1 deficient mouse embryonic fibroblasts (MEF) were used to determine receptor\u2010specific function. Activation of HSC and MEF was assessed using the wound healing assay, Western blotting, and qRT\u2010PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TR\u03b1 and TR\u03b2 expression is downregulated in the liver during hepatic fibrogenesis in humans and mice. TR\u03b1 represents the dominant isoform in HSC. In vitro, T3 blunted TGF\u03b2\u2010induced expression of fibrogenic genes in HSC and abrogated wound healing by modulating TGF\u03b2 signalling, which depended on TR\u03b1 presence. In vivo, TR\u03b1\u2010KO enhanced MCD diet\u2010induced liver fibrogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These observations indicate that TH action in non\u2010parenchymal cells is highly relevant. The interaction of TR\u03b1 with TH regulates the phenotype of HSC via the TGF\u03b2 signalling pathway. Thus, the TH\u2013TR axis may be a valuable target for future therapy of liver fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.15759","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T23:29:07Z","timestamp":1698103747000},"page":"125-138","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Thyroid hormone receptor alpha modulates fibrogenesis in hepatic stellate cells"],"prefix":"10.1111","volume":"44","author":[{"given":"Paul","family":"Manka","sequence":"first","affiliation":[{"name":"Department of Internal Medicine University Hospital Knappschaftskrankenhaus, Ruhr\u2010University Bochum Bochum Germany"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason 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