Transcription Factor CREB3L1 Regulates the Expression of the Sodium/Iodide Symporter (NIS) in Rat Thyroid Follicular Cells

被引:11
作者
Di Giusto, Pablo [1 ,2 ]
Martin, Mariano [1 ,2 ]
Funes Chaban, Macarena [1 ,2 ]
Sampieri, Luciana [1 ,2 ]
Pablo Nicola, Juan [1 ,2 ]
Alvarez, Cecilia [1 ,2 ]
机构
[1] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Bioquim Clin, RA-5000 Cordoba, Argentina
[2] Consejo Nacl Invest Cient & Tecn CIBICI CONICET, Ctr Invest Bioquim Clin & Inmunol, RA-5000 Cordoba, Argentina
关键词
sodium; iodide symporter (NIS); iodide uptake; thyroid follicular cells; cellular homeostasis; endoplasmic reticulum; PAIRED-DOMAIN TRANSCRIPTION; ELEMENT-BINDING PROTEINS; SODIUM-IODIDE SYMPORTER; NA+/I-SYMPORTER; GENE-EXPRESSION; FUNCTIONAL INTERACTION; SECRETORY PATHWAY; UPSTREAM ENHANCER; FACTOR PAX8; CYCLIC-AMP;
D O I
10.3390/cells11081314
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The transcription factor CREB3L1 is expressed in a wide variety of tissues including cartilage, pancreas, and bone. It is located in the endoplasmic reticulum and upon stimulation is transported to the Golgi where is proteolytically cleaved. Then, the N-terminal domain translocates to the nucleus to activate gene expression. In thyroid follicular cells, CREB3L1 is a downstream effector of thyrotropin (TSH), promoting the expression of proteins of the secretory pathway along with an expansion of the Golgi volume. Here, we analyzed the role of CREB3L1 as a TSH-dependent transcriptional regulator of the expression of the sodium/iodide symporter (NIS), a major thyroid protein that mediates iodide uptake. We show that overexpression and inhibition of CREB3L1 induce an increase and decrease in the NIS protein and mRNA levels, respectively. This, in turn, impacts on NIS-mediated iodide uptake. Furthermore, CREB3L1 knockdown hampers the increase the TSH-induced NIS expression levels. Finally, the ability of CREB3L1 to regulate the promoter activity of the NIS-coding gene (Slc5a5) was confirmed. Taken together, our findings highlight the role of CREB3L1 in maintaining the homeostasis of thyroid follicular cells, regulating the adaptation of the secretory pathway as well as the synthesis of thyroid-specific proteins in response to TSH stimulation.
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页数:20
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