Iodinated TG in Thyroid Follicular Lumen Regulates TTF-1 and PAX8 Expression via TSH/TSHR Signaling Pathway.
Our previous study showed that highly iodinated thyroglobulin (TG) inhibited thyroid transcription factor-1 (TTF-1) and paired box gene 8 (PAX8) expression, but the potential mechanism remains unclear. In this study, we constructed a thyroid follicle model in vitro to mimic its natural physiological structure and explored how iodinated TG in the follicular lumen tuned TTF-1 and PAX8 expression. Our data showed that lowly iodinated TG enhanced PKA activity while upregulation of both TTF-1 and PAX8 expression; and that highly iodinated TG triggered PKC activity while suppression of TTF-1 and PAX8 expression. Further, PKA agonist alone could increase TTF-1 and PAX8 expression while PKC agonist decreased TTF-1 and PAX8 level. If blocking PLC-PKC pathway using PKC-specific inhibitor, highly iodinated TG significantly promoted the expressions of TTF-1 and PAX8, and similarly PKA-specific blocker moderately inhibited TTF-1 and PAX8 expression. And opposite tendencies of TTF1 and PAX8 aberrant expression were observed in the condition of low iodinated TG when blocking PLC-PKC and cAMP-PKA signaling pathways. Our results indicated that iodinated TG manipulated TTF-1 and PAX8 expression through PLC-PKC and cAMP-PKA pathways, and highly iodinated TG played inhibitory role via PLC-PKC pathway from the TTF1 and PAX8 perspective while low level of iodinated TG was an activator through cAMP-PKA pathway. Our findings proved that iodinated TG in thyroid follicular lumen regulated TTF-1 and PAX8 expression through thyroid stimulating hormone/thyroid stimulating hormone receptor (TSH/TSHR) mediated cAMP-PKA and PLC-PKC signaling pathways. J. Cell. Biochem. 118: 3444-3451, 2017. © 2017 Wiley Periodicals, Inc.
Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China.
Huibin
0000-0001-6487-7029
H
Huang
Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China.
Yaxiong
Y
Shi
Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China.
Bo
B
Liang
Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China.
Huiyao
H
Cai
Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China.
Qingyan
Q
Cai
D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D000072636:PAX8 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013954:Thyroglobulin / Q000235:genetics / Q000378:metabolism*; D013972:Thyrotropin / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D011989:Receptors, Thyrotropin; C504003:TTF1 protein, human; D014157:Transcription Factors; D013972:Thyrotropin; D013954:Thyroglobulin
IODINATED TG; PAX8; TSH; TSHR; TTF-1