ArticleThe Journal of clinical investigation2017
GLIS3 is indispensable for TSH/TSHR-dependent thyroid hormone biosynthesis and follicular cell proliferation.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- [Clinical guideline of «congenital hypothyroidism»].Problemy endokrinologii · 2022Guideline
- Glis3 Is a Modifier of Cyst Progression in Autosomal Dominant Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2026Article
- GLIS3, a novel regulator of eicosanoid gene expression and metabolism in normal kidney and polycystic kidney disease.Biochemical pharmacology · 2026Article
- Regulation of PKM2 expression and function by GLIS3 during metabolic reprogramming in polycystic kidneys.Experimental & molecular medicine · 2026Article
- Methyltransferase like 3 promotes thyroid folliculogenesisJournal of translational internal medicine · 2026Article
- Glis3 as a critical regulator of Pit1-lineages and renal functions.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Alternative Splicing (AS) Provides an Alternative Mechanism for Regulating GLIS3 Expression and Activity.Cells · 2025Article
- Harnessing endogenous miRNA targeting ZIKV: A cutting-edge strategy to inhibit virus infection.Molecular therapy. Nucleic acids · 2025Article
- Genetics of primary congenital hypothyroidism: three decades of discoveries and persisting etiological challenges.European thyroid journal · 2025Review
- Primary congenital hypothyroidism: a clinical review.Frontiers in endocrinology · 2025Review
- GLIS3: A novel transcriptional regulator of mitochondrial functions and metabolic reprogramming in postnatal kidney and polycystic kidney disease.Molecular metabolism · 2024Article
- STAT6 blockade ameliorates thyroid function in Graves' disease via downregulation of the sodium/iodide symporter.Endocrine connections · 2024Article
- Circulating pancreatic enzyme levels are a causal biomarker of type 1 diabetes.medRxiv : the preprint server for health sciences · 2024Article
- A case of hyalinizing trabecular tumor of the thyroid: diagnostic significance of PAX8-GLIS3 fusion.Thyroid research · 2024Article
- Prevalence of DICER1 variants in large multinodular goiter: thyroid function, clinical and imaging characteristics.Archives of endocrinology and metabolism · 2024Article
- GLIS3 expression in the thyroid gland in relation to TSH signaling and regulation of gene expression.Cellular and molecular life sciences : CMLS · 2024Article
- Kidney and blood pressure regulation-latest evidence for molecular mechanisms.Clinical kidney journal · 2023Review
- Iodine and Thyroid Maternal and Fetal Metabolism during Pregnancy.Metabolites · 2023Review
- Modulation of EZH2 Activity Induces an Antitumoral Effect and Cell Redifferentiation in Anaplastic Thyroid Cancer.International journal of molecular sciences · 2023Article
- GLIS3 regulates transcription of thyroid hormone biosynthetic genes in coordination with other thyroid transcription factors.Cell & bioscience · 2023Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Deficiency in Krüppel-like zinc finger transcription factor GLI-similar 3 (GLIS3) in humans is associated with the development of congenital hypothyroidism. However, the functions of GLIS3 in the thyroid gland and the mechanism by which GLIS3 dysfunction causes hypothyroidism are unknown. In the current study, we demonstrate that GLIS3 acts downstream of thyroid-stimulating hormone (TSH) and TSH receptor (TSHR) and is indispensable for TSH/TSHR-mediated proliferation of thyroid follicular cells and biosynthesis of thyroid hormone. Using ChIP-Seq and promoter analysis, we demonstrate that GLIS3 is critical for the transcriptional activation of several genes required for thyroid hormone biosynthesis, including the iodide transporters Nis and Pds, both of which showed enhanced GLIS3 binding at their promoters. The repression of cell proliferation of GLIS3-deficient thyroid follicular cells was due to the inhibition of TSH-mediated activation of the mTOR complex 1/ribosomal protein S6 (mTORC1/RPS6) pathway as well as the reduced expression of several cell division-related genes regulated directly by GLIS3. Consequently, GLIS3 deficiency in a murine model prevented the development of goiter as well as the induction of inflammatory and fibrotic genes during chronic elevation of circulating TSH. Our study identifies GLIS3 as a key regulator of TSH/TSHR-mediated thyroid hormone biosynthesis and proliferation of thyroid follicular cells and uncovers a mechanism by which GLIS3 deficiency causes neonatal hypothyroidism and prevents goiter development.
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