TGF-beta control of rat thyroid follicular cells differentiation.
TGF-beta1 is a potent inhibitor of growth and DNA synthesis in thyroid cells. It has also been shown that TGF-beta1 inhibits thyrocyte function. The functional inhibition is represented by a downregulation of thyroid specific genes, such as Na(+)/I(-) symporter (NIS), thyroglobulin (TG) and thyroperoxidase (TPO). The transcriptional control of these genes is mediated by thyroid-specific transcription factors: thyroid transcription factor-1 (TTF-1) and PAX-8. It has been shown that Smad proteins play a pivotal role in the intracellular signal transduction of the TGF-beta family members. In this paper, the functional relevance of Smad4, in the control of thyroid differentiation genes and thyroid-specific transcription factors, has been investigated. The data obtained provides, for the first time, evidence that D.N. Smad4-100T is capable of blocking TGF-beta1 action in the regulation of thyroid-specific genes expression. Such action is possible by blocking nuclear translocation of Smad4 and Smad2.
Nicolussi
Arianna
A
Department of Experimental Medicine and Pathology, University 'La Sapienza', v.le Regina Elena 324, 00161, Rome, Italy
D'Inzeo
Sonia
S
Santulli
Maria
M
Colletta
Giulia
G
Coppa
Anna
A
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000502:physiology; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002999:Clone Cells; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D005822:Genetic Vectors / Q000235:genetics; D007150:Immunohistochemistry; D007453:Iodide Peroxidase / Q000235:genetics / Q000502:physiology; D033862:Iron-Binding Proteins / Q000235:genetics / Q000502:physiology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D010766:Phosphorylation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051899:Smad2 Protein; D051901:Smad4 Protein; D027981:Symporters / Q000235:genetics / Q000502:physiology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects*; D000074482:Thyroid Nuclear Factor 1; D013972:Thyrotropin / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology; D053773:Transforming Growth Factor beta1; D000099209:Sodium-Iodide Symporters
D001324:Autoantigens; D003546:Cysteine Endopeptidases; D004268:DNA-Binding Proteins; D007453:Iodide Peroxidase; D033862:Iron-Binding Proteins; D008156:Luciferases; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D011993:Recombinant Fusion Proteins; D051899:Smad2 Protein; D051901:Smad4 Protein; D027981:Symporters; D000074482:Thyroid Nuclear Factor 1; D013972:Thyrotropin; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000099209:Sodium-Iodide Symporters; C000614412:NKX2-1 protein, human; C000614416:Nkx2-1 protein, rat; C499497:Pax8 protein, rat; C497784:Smad2 protein, rat; C490811:Smad4 protein, rat; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; C056658:TPO protein, human; C056657:cysteine proteinase I