التفاصيل البيبلوغرافية
| العنوان: |
Over-expression of LMP2 has a critical role in the pathogenesis of Hürthle cell and hypothyroidism: A novel target of therapy for Hashimoto's thyroiditis. |
| المؤلفون: |
Kimura, Hiroaki, Landek-Salgado, Melissa, Suzuki, Koichi, Rose, Noel R., Caturegli, Patrizio |
| المصدر: |
FASEB Journal; Apr2008 Supplement S2, Vol. 22, p590-590, 1p |
| مستخلص: |
Hürthle cells, found in Hashimoto thyroiditis, Graves' disease, and some forms of thyroid cancer, are thyrocytes characterized by marked eosinophilia and richness in mitochondria. Their pathogenesis remains poorly understood. Thyrocytes of transgenic mice expressing interferon-gamma specifically in the thyroid gland develop a morphology reminiscent of the human Hürthle cell. This morphology is associated with primary hypothyroidism and an increased expression of immunoproteasome genes, mainly LMP2 (low molecular-weight protein 2), and LMP7. We assessed whether blockade of immunoproteasome could ameliorate the Hürthle cell phenotype, using both pharmacologic and genetic means. Interferon-gamma transgenic mice treated with MLN-273 (a proprietary proteasome inhibitor developed by Millenium Pharmaceutical Inc., Boston, MA), showed an improved thyroid morphology. Transgenic mice crossed to LMP2 knockout mice restored a normal thyroid morphology and corrected the hypothyrodism. No effect was noted upon cross with LMP7 knockout mice. Prompted by the mouse results, we studied the expression of LMP2 in thyroid from patients with Hürthle cells and found an increased expression. Our results highlight the role of LMP2 in the ontogeny of Hürthle cells and the accompanying hypothyrodism, proposing LMP2 as a new therapeutic target for treating Hürthle cell lesions. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
