Fabbri Sergio, Zonefrati Roberto, Galli Gianna, Gronchi Giorgio, Perigli Giuliano, Borrelli Andrea, Brandi Maria Luisa
Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
Department of Neuroscience, Psychology, Drug Research & Child Health, University of Florence, Florence, Italy.
J Endocr Soc. 2020 May 25;4(7):bvaa058. doi: 10.1210/jendso/bvaa058. eCollection 2020 Jul 1.
The expression of the parathyroid transcription factors, encoded by the genes , , and , persists after parathyroid morphogenesis. This suggests a role of these genes in the regulatory program that governs parathyroid function in the adult. Indeed, these 3 genes form a transcriptional cascade able to activate gene expression.
Adult adenoma parathyroid tissues were put in primary cell culture to evaluate the messenger ribonucleic acid (mRNA) expression of the gene, of the genes involved in the calcium regulatory signaling pathway (, , and ), and of the 3 genes (, , and involved in the parathyroid morphogenesis in the presence of different extracellular calcium concentrations from 0.1 mM to 3.0 mM.
The aim of the study was to investigate whether different extracellular calcium conditions could control the expression of transcription factors critical for parathyroid embryogenesis.
The results of the experiments showed that the mRNA expression of , , and genes follows the same response as the gene to extracellular calcium concentrations, with the highest expression at low calcium (0.1 mM) and the lowest at high calcium (3.0 mM). Conversely, the genes involved in the calcium signaling in the parathyroid cells showed a variable response to the extracellular calcium concentrations, with the and genes exhibiting a sensitivity to low calcium concentrations.
These findings indicate that transcription factors recognized for their role in parathyroid embryogenesis show a response to extracellular calcium later in adulthood that parallels the behavior of the gene.
由基因Gcm2、GATA2和Eya1编码的甲状旁腺转录因子的表达在甲状旁腺形态发生后持续存在。这表明这些基因在调控成年甲状旁腺功能的程序中发挥作用。事实上,这三个基因形成了一个能够激活PTH基因表达的转录级联反应。
将成年腺瘤甲状旁腺组织进行原代细胞培养,以评估PTH基因、参与钙调节信号通路的基因(CaSR、TRPV5和PMCA1b)以及在0.1 mM至3.0 mM不同细胞外钙浓度下参与甲状旁腺形态发生的三个基因(Gcm2、GATA2和Eya1)的信使核糖核酸(mRNA)表达。
本研究的目的是调查不同的细胞外钙条件是否能控制对甲状旁腺胚胎发育至关重要的转录因子的表达。
实验结果表明,Gcm2、GATA2和Eya1基因的mRNA表达对细胞外钙浓度的反应与PTH基因相同,在低钙(0.1 mM)时表达最高,在高钙(3.0 mM)时表达最低。相反,甲状旁腺细胞中参与钙信号传导的基因对细胞外钙浓度表现出可变反应,CaSR和TRPV5基因对低钙浓度敏感。
这些发现表明,在甲状旁腺胚胎发育中发挥作用的转录因子在成年后期对细胞外钙的反应与PTH基因的行为相似。