Hormonal regulation of FoxE1 expression in thyroid epithelial cells

Abstract

Resumen del póster presentado al 38th Annual Meeting of the European Thyroid Association celebrado en Santiago de Compostela (España) del 6 al 10 de septiembre de 2014.Differentiation of thyroid follicular cells is regulated by hormones and growth factors. Among these signals, TSH, IGF1 and TGF play a predominant role. These three ligands transcriptionally regulate markers of thyroid differentiation such as Thyroglobulin (Tg) Thyroperoxidase (TPO) and sodium iodide symporter (NIS). This effect takes place, at least in part, through a responsive element to where the FoxE1 binds, opening chromatin and creating an environment that facilitate the binding of other transcription factors. Taking in consideration the proposed role of FoxE1 as a mediator of the hormone/growth factor transcriptional action, the main objective of this work was to study the regulation of FoxE1 expression by TSH, IGF1 and TGFβ. Mouse FoxE1 promoter was cloned and transient transfections were performed in PCCL3 in presence or absence of TSH, IGF1 and TGFβ. Forskolin and H89 were used to study the cAMP/PKA pathway. Co-transfections in Hela cells were performed to elucidate the role of other transcription factors. FoxE1 protein and mRNA levels in different conditions were evaluated by westernblot and RT-qPCR. The in silico analysis of FoxE1 promoter reveals the presence of a CRE and several Smad binding sites in its sequence. TSH and IGF1 induce the transcription of FoxE1 by the activation of its promoter. The TSH effect is cAMP/ PKA dependent and therefore CREB positively regulates FoxE1 transcription. IGF1 cooperates with TSH while TGF inhibits the TSH induction on FoxE1 gene expression. Not effect was found of TGF on IGF1 action. We conclude that there is a complex network of signals and transcription factors involved in FoxE1 expression that are essential to maintain a fine regulation of this important gene that control thyroid cell differentiation.Peer reviewe