Document Detail


TGF-beta promotes thyroid epithelial cell hyperplasia and fibrosis in IFN-gamma-deficient NOD.H-2h4 mice.
MedLine Citation:
PMID:  18641364     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
IFN-gamma(-/-)NOD.H-2h4 mice given 0.05% NaI in their water develop severe thyroid epithelial cell (thyrocyte) hyperplasia and proliferation (TEC H/P) and fibrosis. Proliferating thyrocytes of IFN-gamma(-/-) mice with TEC H/P produce TGF-beta as demonstrated by immunohistochemical staining and in situ hybridization. Strong expression of activating phosphorylated Smad-2/3 and weak expression of inhibitory Smad-7 by proliferating thyrocytes correlate with the severity of TEC H/P. Splenocytes from IFN-gamma(-/-) mice with severe TEC H/P transfer severe TEC H/P to IFN-gamma(-/-)NOD.H-2h4.SCID mice. Mice given anti-TGF-beta had markedly reduced thyrocyte proliferation and decreased fibrosis compared with mouse Ig-treated controls, suggesting that TGF-beta plays an important role in development of TEC H/P induced by activated splenocytes. Moreover, transgenic IFN-gamma(-/-)NOD.H-2h4 mice expressing TGF-beta on thyrocytes all develop fibrosis and moderate to severe TEC H/P with accelerated kinetics, directly demonstrating a role for TGF-beta in severe TEC H/P and fibrosis.
Authors:
Shiguang Yu; Gordon C Sharp; Helen Braley-Mullen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  181     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-21     Completed Date:  2008-08-19     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2238-45     Citation Subset:  AIM; IM    
Affiliation:
Department of Veterans Affairs Research Service, Columbia, MO 65212, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / immunology
Cell Proliferation
Epithelial Cells / cytology,  metabolism*
Fibrosis / genetics,  metabolism,  pathology
Interferon-gamma / deficiency*,  genetics,  metabolism*
Mice
Mice, Inbred NOD
Mice, Knockout
Phosphorylation
Protein-Serine-Threonine Kinases / metabolism
Receptors, Transforming Growth Factor beta / metabolism
Smad2 Protein / metabolism
Smad3 Protein / metabolism
Spleen / immunology,  metabolism
Thymus Hyperplasia / genetics,  metabolism*,  pathology*
Transforming Growth Factor beta / genetics,  immunology,  metabolism*
Chemical
Reg. No./Substance:
0/Antibodies; 0/Receptors, Transforming Growth Factor beta; 0/Smad2 Protein; 0/Smad2 protein, mouse; 0/Smad3 Protein; 0/Smad3 protein, mouse; 0/Transforming Growth Factor beta; 82115-62-6/Interferon-gamma; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.30/transforming growth factor-beta type II receptor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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