{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:52:38Z","timestamp":1787237558963,"version":"build-2736575974"},"reference-count":74,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Pathological conditions of the thyroid hormone (TH) system are routinely diagnosed by using serum concentrations of thyrotropin (TSH), which is sufficient in most cases. However, in certain conditions, such as resistance to TH due to mutations in\n                      <jats:italic toggle=\"yes\">THRB<\/jats:italic>\n                      (RTHb) or TSH-releasing pituitary adenoma (TSHoma), TSH may be insufficient for a correct diagnosis, even in combination with serum TH concentrations. Likewise, under TH replacement therapy, these parameters can be misleading and do not always allow optimal treatment. Hence, additional biomarkers to assess challenging clinical conditions would be highly beneficial.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Data from untargeted multi-omics analyses of plasma samples from experimental thyrotoxicosis in human and mouse were exploited to identify proteins that might represent possible biomarkers of TH function. Subsequent mouse studies were used to identify the tissue of origin and the involvement of the two different TH receptors (TR). For in-depth characterization of the underlying cellular mechanisms, primary mouse cells were used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The analysis of the plasma proteome data sets revealed 16 plasma proteins that were concordantly differentially abundant under thyroxine treatment compared with euthyroid controls across the two species. These originated predominantly from liver, spleen, and bone. Independent studies in a clinical cohort and different mouse models identified CD5L as the most robust putative biomarker under different serum TH states and treatment periods.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      studies revealed that CD5L originates from proinflammatory M1 macrophages, which are similar to liver-residing Kupffer cells, and is regulated by an indirect mechanism requiring the secretion of a yet unknown factor from hepatocytes. In agreement with the role of TR\u03b11 in immune cells and the TR\u03b2-dependent hepatocyte-derived signaling, the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      regulation of\n                      <jats:italic toggle=\"yes\">Cd5l<\/jats:italic>\n                      expression depended on both TR isoforms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our results identify several novel targets of TH action in serum, with CD5L as the most robust marker. Although further studies will be needed to validate the specificity of these targets, CD5L seems to be a promising candidate to assess TH action in hepatocyte-macrophage crosstalk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2019.0635","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T08:35:46Z","timestamp":1584520546000},"page":"908-923","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["CD5L Constitutes a Novel Biomarker for Integrated Hepatic Thyroid Hormone Action"],"prefix":"10.1177","volume":"30","author":[{"given":"Sebastian","family":"Nock","sequence":"first","affiliation":[{"name":"Department of Molecular Endocrinology, Center of Brain, Behavior and Metabolism, Institute for Endocrinology and Diabetes, University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kornelia","family":"Johann","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, Center of Brain, Behavior and Metabolism, Institute for Endocrinology and Diabetes, University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisbeth","family":"Harder","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, Center of Brain, Behavior and Metabolism, Institute for Endocrinology and Diabetes, University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Katrin","family":"Wirth","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Endokrinologie, Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, CVK, Berlin, Germany."},{"name":"Medizinische Klinik f\u00fcr Endokrinologie und Stoffwechselmedizin, Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany."},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kostja","family":"Renko","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Endokrinologie, Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, CVK, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin S.","family":"Hoefig","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Endokrinologie, Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, CVK, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Kracke","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Hackler","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Experimentelle Endokrinologie, Charit\u00e9-Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, CVK, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Engelmann","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Rauner","sequence":"additional","affiliation":[{"name":"Department of Medicine III; 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