ArticlePloS one2009
Immunoproteasome overexpression underlies the pathogenesis of thyroid oncocytes and primary hypothyroidism: studies in humans and mice.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- The role of proteasomes in tumorigenesis.Genes & diseases · 2024Review
- Construction of the coexpression network involved in the pathogenesis of thyroid eye disease via bioinformatics analysis.Human genomics · 2022Article
- Oncocytic Change in Thyroid Pathology.Frontiers in endocrinology · 2021Review
- Immunoproteasome in the blood plasma of children with acute appendicitis, and its correlation with proteasome and UCHL1 measured by SPR imaging biosensors.Clinical and experimental immunology · 2018Article
- Amelioration of autoimmunity with an inhibitor selectively targeting all active centres of the immunoproteasome.British journal of pharmacology · 2018Article
- Immunoproteasome subunit LMP7 Deficiency Improves Obesity and Metabolic Disorders.Scientific reports · 2015Article
- New Insights into the Function of the Immunoproteasome in Immune and Nonimmune Cells.Journal of immunology research · 2015Review
- Hashimoto's thyroiditis: celebrating the centennial through the lens of the Johns Hopkins hospital surgical pathology records.Thyroid : official journal of the American Thyroid Association · 2013Article
- LMP2, a novel immunohistochemical marker to distinguish renal oncocytoma from the eosinophilic variant of chromophobe renal cell carcinoma.Experimental and molecular pathology · 2013Article
- Cell-type-specific expression of STAT transcription factors in tissue samples from patients with lymphocytic thyroiditis.Endocrine pathology · 2012Article
- Hürthle cells predict hypothyroidism in interferon-γ transgenic mice of different genetic backgrounds.Endocrinology · 2012Article
- Oncocytic mania: a review of oncocytic lesions throughout the body.Journal of endocrinological investigation · 2011Review
- The type 1 diabetes - HLA susceptibility interactome--identification of HLA genotype-specific disease genes for type 1 diabetes.PloS one · 2010Article
- A nonclassical model of autoimmune hypothyroidism.Thyroid : official journal of the American Thyroid Association · 2010Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundOncocytes of the thyroid gland (Hürthle cells) are found in tumors and autoimmune diseases. They have a unique appearance characterized by abundant granular eosinophilic cytoplasm and hyperchromatic nucleus. Their pathogenesis has remained, thus far, unknown. METHODOLOGY/PRINCIPAL
findingsUsing transgenic mice chronically expressing IFNgamma in thyroid gland, we showed changes in the thyroid follicular epithelium reminiscent of the human oncocyte. Transcriptome analysis comparing transgenic to wild type thyrocytes revealed increased levels of immunoproteasome subunits like LMP2 in transgenics, suggesting an important role of the immunoproteasome in oncocyte pathogenesis. Pharmacologic blockade of the proteasome, in fact, ameliorated the oncocytic phenotype. Genetic deletion of LMP2 subunit prevented the development of the oncocytic phenotype and primary hypothyroidism. LMP2 was also found expressed in oncocytes from patients with Hashimoto thyroiditis and Hürthle cell tumors. CONCLUSIONS/SIGNIFICANCE: In summary, we report that oncocytes are the result of an increased immunoproteasome expression secondary to a chronic inflammatory milieu, and suggest LMP2 as a novel therapeutic target for the treatment of oncocytic lesions and autoimmune hypothyroidism.
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