Endocrine Abstracts

Sox9 is a transcription factor of the HMG box DNA binding family involved in chondrocyte differentiation, sexual determination and the development of endoderm-derived-organs. Preliminary results from our laboratory have shown that Sox9 is expressed in the thyroid gland and its regulation is under the control of TSH and TGFβ. In this work we studied the role of Sox9 in the thyroid cells differentiation and its relationship with the other thyroid transcription factors, mainly with FoxE1, an important transcription factor essential for the development and differentiation of the thyroid gland.

Sox9 and FoxE1 mRNA and protein levels were determined by RT-qPCR and Western-blot respectively. Co-transfections assays with FoxE1 promoter and Sox9 expression vector were performed in Hela cells to elucidate the role of Sox9 in the regulation of Foxe1 expression. The binding capacity of Sox9 to its DNA consensus sequence in the rat Foxe1 promoter was analyzed by Electrophoretic Mobility Shift Assays (EMSA). Sox9 was silenced in PCCl3 cells using specific siRNA.

By in silico analysis we have observed a Sox9 consensus DNA sequence within the FoxE1 promoter, to which recombinant Sox9 protein efficiently binds. Furthermore, we have demonstrated that Sox9 is functional as it was able to induce four fold the transcriptional activity of FoxE1 promoter. Finally, the inhibition of Sox9 led to a drastic decrease in the expression levels of FoxE1.

These results show that Sox9 is a transcription factor upstream of FoxE1 and involved in its regulation in differentiated thyroid follicular cells. Considering the important role of FoxE1 in the pathophysiology of the thyroid gland these results encourage to think that Sox9 could play an important role in the regulation of development and differentiation of the thyroid gland.