{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T14:12:24Z","timestamp":1784297544342,"version":"3.55.0"},"reference-count":45,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,11,1]]},"abstract":"<jats:p>CD34+ fibrocytes are bone marrow\u2013derived monocyte progenitor cells that traffic to sites of tissue injury and repair. They putatively infiltrate the orbit in thyroid-associated ophthalmopathy where they appear to transition into CD34+ orbital fibroblasts (OFs) that interact with residential CD34\u2212 fibroblasts. A unique phenotypic attribute of fibrocytes and CD34+ OFs is their expression of the functional thyrotropin receptor (TSHR) and other \u201cthyroid-specific\u201d proteins. When activated through TSHR, fibrocytes express a number of cytokines and other inflammatory genes. Here we sought to determine whether pentraxin-3 (PTX-3), an acute-phase protein involved in inflammation and autoimmunity, might be induced by TSH in fibrocytes and OFs. These cells were collected from patients with Graves disease and healthy individuals. PTX-3 mRNA levels were determined by real-time PCR, protein was determined by ELISA and Western blot, and PTX-3 gene promoter activity was assessed with reporter assays. PTX-3 expression was induced by TSH in both cell types, regardless of the health status of the donor and was a consequence of increased steady-state PTX-3 mRNA levels. M22, a TSHR-activating monoclonal antibody, also induced PTX-3. The induction could be attenuated by dexamethasone and by IGF-I receptor\u2013blocking antibodies, teprotumumab and 1H7. TSH effects were mediated through phosphatidylinositol 3-kinase\/AKT, mammalian target of rapamycin\/p70s6k, Janus tyrosine kinase 2 pathways, and enhanced PTX-3 mRNA stability. These findings indicate that PTX-3 is a TSH target gene, the expression of which can be induced in fibrocytes and OFs. They suggest that PTX-3 might represent a previously unidentified nexus between the thyroid axis and the mechanisms involved in tissue remodeling.<\/jats:p>","DOI":"10.1210\/en.2015-1399","type":"journal-article","created":{"date-parts":[[2015,8,19]],"date-time":"2015-08-19T17:00:42Z","timestamp":1440003642000},"page":"4336-4344","source":"Crossref","is-referenced-by-count":27,"title":["Pentraxin-3 Is a TSH-Inducible Protein in Human Fibrocytes and Orbital Fibroblasts"],"prefix":"10.1210","volume":"156","author":[{"given":"Hao","family":"Wang","sequence":"first","affiliation":[{"name":"Departments of Ophthalmology and Visual Sciences (H.W., S.J.A., R.F., T.J.S.), University of Michigan Medical School, Ann Arbor, Michigan 48105"},{"name":"Department of Ophthalmology (H.W., R.-L.W.), Shanghai Changzheng Hospital, Second Military Medical University, 200003 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Atkins","sequence":"first","affiliation":[{"name":"Departments of Ophthalmology and Visual Sciences (H.W., S.J.A., R.F., T.J.S.), University of Michigan Medical School, Ann Arbor, Michigan 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshini","family":"Fernando","sequence":"first","affiliation":[{"name":"Departments of Ophthalmology and Visual Sciences (H.W., S.J.A., R.F., T.J.S.), University of Michigan Medical School, Ann Arbor, Michigan 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Li","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Ophthalmology (H.W., R.-L.W.), Shanghai Changzheng Hospital, Second Military Medical University, 200003 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry J.","family":"Smith","sequence":"first","affiliation":[{"name":"Departments of Ophthalmology and Visual Sciences (H.W., S.J.A., R.F., T.J.S.), University of Michigan Medical School, Ann Arbor, Michigan 48105"},{"name":"Division of Metabolism (T.J.S.), Endocrinology, and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2015,8,19]]},"reference":[{"key":"2020071612082355300_B1","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1056\/NEJMcp0801880","article-title":"Clinical practice. 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