Thyroid hormones regulate gene expression via both canonical and non-canonical signaling. Hyperthyroidism is associated with elevated plasma levels of fibronectin (FN): in this study we elucidate the molecular mechanism through which triiodothyronine (T3) regulates FN and demonstrate that T3 induces FN expression via a non-canonical pathway by activating hypoxia-inducible factor-1 (HIF-1). We found that T3 treatment increased cellular and secreted FN in human hepatoma cells (HepG2) and human dermal fibroblasts (HF) via the PI3K/Akt/HIF-1 pathway. The inhibition of either Akt phosphorylation with wortmannin or HIF-1 with YC1 in both cell types prevented HIF-1α synthesis and FN positive regulation upon T3 treatment. We showed that HIF-1α overexpression per se was sufficient to up-regulate FN in both cell lines as demonstrated by the transient transfection of both the constitutively active and wild-type forms of HIF-1α. Our data demonstrate the involvement of the PI3K/Akt/HIF-1 pathway in mediating T3 induced FN up-regulation.

Thyroid hormone regulates fibronectin expression through the activation of the hypoxia inducible factor 1 / Taglieri, Ludovica; Nardo, Tiziana; Vicinanza, Roberto; Ross, Jaime M.; Scarpa, Susanna; Coppotelli, Giuseppe. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - 493:3(2017), pp. 1304-1310. [10.1016/j.bbrc.2017.09.169]

Thyroid hormone regulates fibronectin expression through the activation of the hypoxia inducible factor 1

Taglieri, Ludovica;VICINANZA, ROBERTO;SCARPA, Susanna;
2017

Abstract

Thyroid hormones regulate gene expression via both canonical and non-canonical signaling. Hyperthyroidism is associated with elevated plasma levels of fibronectin (FN): in this study we elucidate the molecular mechanism through which triiodothyronine (T3) regulates FN and demonstrate that T3 induces FN expression via a non-canonical pathway by activating hypoxia-inducible factor-1 (HIF-1). We found that T3 treatment increased cellular and secreted FN in human hepatoma cells (HepG2) and human dermal fibroblasts (HF) via the PI3K/Akt/HIF-1 pathway. The inhibition of either Akt phosphorylation with wortmannin or HIF-1 with YC1 in both cell types prevented HIF-1α synthesis and FN positive regulation upon T3 treatment. We showed that HIF-1α overexpression per se was sufficient to up-regulate FN in both cell lines as demonstrated by the transient transfection of both the constitutively active and wild-type forms of HIF-1α. Our data demonstrate the involvement of the PI3K/Akt/HIF-1 pathway in mediating T3 induced FN up-regulation.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11573/1013576
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