Disturbed function of TBL1X has a differential effect on T3-regulated gene expression in two human liver cell models.

Autor:	Hu Y; Endocrine Laboratory, Department of Laboratory Medicine, University of Amsterdam, Amsterdam, the Netherlands.; Research Institute Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, the Netherlands., Soares De Oliveira L; Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston Medical Center, Boston, Massachusetts, USA.; Center for Regenerative Medicine (CReM) of Boston University and Boston Medical Center, Boston, Massachusetts, USA., Falize K; Endocrine Laboratory, Department of Laboratory Medicine, University of Amsterdam, Amsterdam, the Netherlands., Paul van Trotsenburg AS; Research Institute Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, the Netherlands.; Department of Pediatric Endocrinology. Emma children's hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Fliers E; Research Institute Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, the Netherlands.; Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Kaserman JE; Center for Regenerative Medicine (CReM) of Boston University and Boston Medical Center, Boston, Massachusetts, USA.; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA., Wilson AA; Center for Regenerative Medicine (CReM) of Boston University and Boston Medical Center, Boston, Massachusetts, USA.; The Pulmonary Center and Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA., Hollenberg AN; Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston Medical Center, Boston, Massachusetts, USA., Bruinstroop E; Research Institute Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, the Netherlands.; Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Boelen A; Endocrine Laboratory, Department of Laboratory Medicine, University of Amsterdam, Amsterdam, the Netherlands.; Research Institute Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, the Netherlands.
Jazyk:	angličtina
Zdroj:	European thyroid journal [Eur Thyroid J] 2024 Oct 14; Vol. 13 (5). Date of Electronic Publication: 2024 Oct 14 (Print Publication: 2024).
DOI:	10.1530/ETJ-24-0162
Abstrakt:	Background: Mutations in TBL1X, part of the NCOR1/SMRT corepressor complex, were identified in patients with hereditary X-linked central congenital hypothyroidism and associated hearing loss. The role of TBL1X in thyroid hormone (TH) action, however, is incompletely understood. The aim of the present study was to investigate the role of TBL1X on T3-regulated gene expression in two human liver cell models. Methods: A human hepatoma cell line (HepG2) wherein TBL1X was downregulated using siRNAs, and human-induced pluripotent stem cell-derived hepatocytes (iHeps) generated from individuals with a TBL1X N365Y mutation. Both cell types were treated with increasing concentrations of T3. The expression of T3-regulated genes was measured by qPCR. Results: KLF9, CPT1A, and PCK1 mRNA expression were higher upon T3 stimulation in the HepG2 cells with decreased TBL1X expression compared to controls, while DIO1 mRNA expression was lower. Hemizygous TBL1X N365Y iHeps exhibited decreased expression of CPT1A, G6PC1, PCK1, FBP1, and ELOVL2 compared to cells with the heterozygous TBL1X N365Y allele, but KLF9 and HMGCS2 expression was unaltered. Conclusion: Downregulation of TBL1X in HepG2 cells and the TBL1X N365Y variant in iHeps have differential effects on T3-regulated gene expression. This suggests that TBL1X may play a gene context role in TH action.
Databáze:	MEDLINE
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