Pioglitazone, a PPARγ agonist, upregulates the expression of caveolin-1 and catalase, essential for thyroid cell homeostasis. A clue to the pathogenesis of Hashimoto's thyroiditis.

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Pioglitazone, a PPARγ agonist, upregulates the expression of caveolin-1 and catalase, essential for thyroid cell homeostasis. A clue to the pathogenesis of Hashimoto's thyroiditis.

Thyroid. 2016 Jun 20;

Authors: Werion A, Joris V, Hepp M, Papasokrati L, Marique L, de Ville de Goyet C, Van Regemorter V, Mourad M, Lengelé B, Daumerie C, Marbaix E, Brichard S, Many MC, Craps J

Abstract
CONTEXT: Peroxisome proliferator-activated receptor γ (PPARγ) is a transcriptional factor that regulates the expression of multiple target genes involved in several metabolic pathways as well as in inflammation. The expression and cell localization of caveolin-1 (Cav-1), thyroid peroxidase (TPO), and dual oxidase (DUOX), involved in the extracellular iodination, is modulated by Th1 cytokines in human normal thyroid cells and in Hashimoto's thyroiditis (HT).
OBJECTIVES: 1) To analyze the PPARγ expression at the follicular level in HT versus controls in correlation with the one of Cav-1, 2) to study the effects of Th1 cytokines on PPARγ and catalase expression in human thyrocytes primary cultures, 3) to study the effects of pioglitazone, a PPAR γ agonist, on thyroxisome's components (Cav-1, TPO, DUOX) and on antioxidant defenses (catalase).
RESULTS: Although the global expression of PPARγ in the whole Hashimoto's glands was not modified as compared to controls, there was a great heterogeneity among glands and among follicles in a same gland. Besides normal type 1 follicles, there were, around inflammatory zones, hyperactive type 2 follicles with high PPARγ and Cav-1 expression and inactive type 3 follicles unable to form T4, which did not express PPARγ nor Cav-1. In human thyrocytes in primary cultures, Th1 cytokines decreased PPARγ and catalase expression; pioglitazone increased Cav-1, TPO and catalase expression.
CONCLUSION: PPARγ plays a central role in normal thyroid physiology by upregulating Cav-1, essential for the thyroxisome's organization and the extracellular iodination. By upregulating catalase, PPARγ also maintains the cell homeostasis. The inhibitory effect of Th1 cytokines on PPARγ expression may be considered as a new pathogenetic mechanism for Hashimoto's thyroiditis and the use of PPARγ agonists could open a new therapeutic approach.

PMID: 27324467 [PubMed - as supplied by publisher]

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