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

DI GIUSTO, P; MARTIN, M; FUNES CHABÁN, M; SAMPIERI, L; NICOLA, JP; ALVAREZ, CI

CELLS (BASEL)

MDPI

Año: 2022

2073-4409

The transcription factor CREB3L1 is expressedin a wide variety of tissues including cartilage, pancreas, and bone. It islocated in the endoplasmic reticulum and upon stimulation is transported to theGolgi where is proteolytically cleaved. Then, the N-terminal domaintranslocates to the nucleus to activate gene expression. In thyroid follicularcells, CREB3L1 is a downstream effector of thyrotropin (TSH), promoting theexpression of proteins of the secretory pathway along with an expansion of theGolgi volume. Here, we analyzed the role of CREB3L1 as a TSH-dependenttranscriptional regulator of the expression of the sodium/iodide symporter(NIS), a major thyroid protein that mediates iodide uptake. We show thatoverexpression and inhibition of CREB3L1 induce an increase and decrease in theNIS protein and mRNA levels, respectively. This, in turn, impacts on NIS-mediated iodideuptake. Furthermore, CREB3L1 knockdown hampers the increase the TSH-induced NIS expressionlevels. Finally, the ability of CREB3L1 to regulate the promoteractivity of the NIS-codinggene (Slc5a5) was confirmed. Taken together, our findings highlight the role ofCREB3L1 in maintaining the homeostasis of thyroid follicular cells, regulatingthe adaptation of the secretory pathway as well as the synthesis ofthyroid-specific proteins in response to TSH stimulation.