The transcription factor NF-κB mediates thyrotropinstimulated expression of thyroid differentiation markers

GEYSELS, ROMINA CELESTE; PEYRET, VICTORIA; MARTÍN, MARIANO; NAZAR, MAGALÍ; REALE, CARLA; BERNAL BARQUERO, CARLOS EDUARDO; MIRANDA, LUCAS; MARTI, MARCELO ADRIAN ; VITO, PASQUALE; MASINI-REPISO, ANA M.; NICOLA, JUAN PABLO

THYROID

MARY ANN LIEBERT INC

Lugar: New York; Año: 2020

1050-7256

ackground: The Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factor is a key regulator of cell survival, proliferation and gene expression. Although activation of NF-κB signaling in thyroid follicular cells following thyrotropin (TSH) receptor (TSHR) engagement has been reported, the downstream signaling leading to NFκB activation remains unexplored. Here, we sought to elucidate the mechanisms that regulate NF-κB signaling activation in response to TSH stimulation. Methods: Fisher rat-derived thyroid cell lines and primary cultures of NFκB essential modulator (NEMO)-deficient mice thyrocytes were used as models. Signaling pathways leading to the activation of NF-κB were investigated using chemical inhibitors and phospho-specific antibodies. Luciferase reporter gene assays and site-directed mutagenesis were used to monitor NF-κB-dependent gene transcriptional activity and the expression of thyroid differentiation