| Human fibrocytes coexpress thyroglobulin and thyrotropin receptor. | |
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MedLine Citation:
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PMID: 22517745 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thyroglobulin (Tg) is the macromolecular precursor of thyroid hormones and is thought to be uniquely expressed by thyroid epithelial cells. Tg and the thyroid-stimulating hormone receptor (TSHR) are targets for autoantibody generation in the autoimmune disorder Graves disease (GD). Fully expressed GD is characterized by thyroid overactivity and orbital tissue inflammation and remodeling. This process is known as thyroid-associated ophthalmopathy (TAO). Early reports suggested that in TAO, both Tg and TSHR become overexpressed in orbital tissues. Previously, we found that CD34(+) progenitor cells, known as fibrocytes, express functional TSHR, infiltrate the orbit, and comprise a large subset of orbital fibroblasts in TAO. We now report that fibrocytes also express Tg, which resolves as a 305-kDa protein on Western blots. It can be immunoprecipitated with anti-Tg Abs. Further, (125)iodine and [(35)S]methionine are incorporated into Tg expressed by fibrocytes. De novo Tg synthesis is attenuated with a specific small interfering RNA targeting the protein. A fragment of the Tg gene promoter fused to a luciferase reporter exhibits substantial activity when transfected into fibrocytes. Unlike fibrocytes, GD orbital fibroblasts, which comprise a mixture of CD34(+) and CD34(-) cells, express much lower levels of Tg and TSHR. When sorted into pure CD34(+) and CD34(-) subsets, Tg and TSHR mRNA levels become substantially higher in CD34(+) cells. These findings indicate that human fibrocytes express multiple "thyroid-specific" proteins, the levels of which are reduced after they infiltrate tissue. Our observations establish the basis for Tg accumulation in orbital GD. |
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Authors:
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Roshini Fernando; Stephen Atkins; Nupur Raychaudhuri; Ying Lu; Bin Li; Raymond S Douglas; Terry J Smith |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-04-19 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 109 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-05-09 Completed Date: 2012-08-13 Revised Date: 2013-02-19 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 7427-32 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, MI 48105, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD34
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metabolism Antigens, CD45 / metabolism Blotting, Western Cells, Cultured Connective Tissue Cells / metabolism Fibroblasts / metabolism* Gene Expression Graves Ophthalmopathy / genetics, metabolism, pathology Humans Immunohistochemistry Mesenchymal Stromal Cells / metabolism* Orbit / metabolism RNA Interference RNA, Messenger / genetics, metabolism Receptors, Thyrotropin / genetics, metabolism* Reverse Transcriptase Polymerase Chain Reaction Thyroglobulin / genetics, metabolism* Thyroid Gland / cytology, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK063121/DK/NIDDK NIH HHS; EY007003/EY/NEI NIH HHS; EY011708/EY/NEI NIH HHS; EY021197/EY/NEI NIH HHS; EY08976/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD34; 0/RNA, Messenger; 0/Receptors, Thyrotropin; 9010-34-8/Thyroglobulin; EC 3.1.3.48/Antigens, CD45 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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