Thyrotropin regulation of differentiated gene transcription in adult human thyrocytes in primary culture.
Thyrotropin regulation of differentiated gene transcription in adult human thyrocytes in primary culture.
复制标题
DOI：
10.1016/j.mce.2020.111032
复制
发表时间：
2020-12-01
影响因子：
4.1
通讯作者：
Gershengorn MC
中科院分区：
文献类型：
--
作者：
Jang D;Marcus-Samuels B;Morgan SJ;Klubo-Gwiezdzinska J;Neumann S;Gershengorn MC
甲状腺转录因子（TTF）-NKX 2 -1，FOXE 1，PAX 8和HHEX -调节参与小鼠甲状腺发育的多个基因，但对甲状腺特异性基因-甲状腺球蛋白（TG），甲状腺过氧化物酶（TPO），脱碘酶2型（DIO 2），钠/碘同向转运体（NIS）和TSH受体（TSHR）-在成人甲状腺细胞中的TTF调节知之甚少。促甲状腺激素（促甲状腺激素，TSH）对人甲状腺细胞原代培养物中甲状腺特异性基因表达的调节是双相的，产生一个倒U形剂量反应曲线（IUDRC），在低剂量下上调，在高剂量下下调。在此，我们表明，NKX 2 -1，FOXE 1和PAX 8是TSH诱导的TG，TPO，DIO 2，NIS和TSHR的mRNA水平上调所必需的，而HHEX对这些甲状腺特异性基因mRNA的水平几乎没有影响。我们表明，促甲状腺激素诱导的上调是介导的变化，在他们的转录，而不是在他们的mRNA降解的变化。与甲状腺特异性基因的IUDRC相反，TSH对NKX 2 -1、FOXE 1和PAX 8的mRNA水平的影响在高剂量TSH下表现出双相降低，而TSH对HHEX mRNA水平的调节表现出与甲状腺特异性基因的IUDRC重叠的IUDRC。与小鼠发育过程中的发现相反，TTF对成人甲状腺细胞中其他TTF mRNA的水平没有重大影响。因此，我们发现在小鼠发育中甲状腺特异性基因的调节和在成人甲状腺细胞中这些基因的TSH调节的相似性和重要差异。
Thyroid transcription factors (TTFs) - NKX2-1, FOXE1, PAX8 and HHEX - regulate multiple genes involved in thyroid development in mice but little is known about TTF regulation of thyroid-specific genes - thyroglobulin (TG), thyroid peroxidase (TPO), deiodinase type 2 (DIO2), sodium/iodide symporter (NIS) and TSH receptor (TSHR) - in adult, human thyrocytes. Thyrotropin (thyroid-stimulating hormone, TSH) regulation of thyroid-specific gene expression in primary cultures of human thyrocytes is biphasic yielding an inverted U-shaped dose-response curve (IUDRC) with upregulation at low doses and decreases at high doses. Herein we show that NKX2-1, FOXE1 and PAX8 are required for TSH-induced upregulation of the mRNA levels of TG, TPO, DIO2, NIS, and TSHR whereas HHEX has little effect on the levels of these thyroid-specific gene mRNAs. We show that TSH-induced upregulation is mediated by changes in their transcription and not by changes in the degradation of their mRNAs. In contrast to the IUDRC of thyroid-specific genes, TSH effects on the levels of the mRNAs for NKX2-1, FOXE1 and PAX8 exhibit monophasic decreases at high doses of TSH whereas TSH regulation of HHEX mRNA levels exhibits an IUDRC that overlaps the IUDRC of thyroid-specific genes. In contrast to findings during mouse development, TTFs do not have major effects on the levels of other TTF mRNAs in adult, human thyrocytes. Thus, we found similarities and important differences in the regulation of thyroid-specific genes in mouse development and TSH regulation of these genes in adult, human thyrocytes.
登录
查看更多内容
DOI：
10.1007/978-1-4939-8600-2_1
发表时间：
2018
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Morgan SJ;Neumann S;Gershengorn MC
通讯作者：
Gershengorn MC
影响因子：
5.6
作者：
Calabrese EJ
通讯作者：
Calabrese EJ
影响因子：
3.7
作者：
Fernández LP;López-Márquez A;Martínez AM;Gómez-López G;Santisteban P
通讯作者：
Santisteban P
影响因子：
5.8
作者：
Sahin, M;Allard, BL;McIver, B
通讯作者：
McIver, B
影响因子：
4.8
作者：
Oguchi, H;Kimura, S
通讯作者：
Kimura, S