Pioglitazone, a PPAR gamma Agonist, Upregulates the Expression of Caveolin-1 and Catalase, Essential for Thyroid Cell Homeostasis: A Clue to the Pathogenesis of Hashimoto's Thyroiditis

作者：Werion Alexis; Joris Virginie; Hepp Michael; Papasokrati Lida; Marique Lancelot; de Goyet Christine de Ville; Van Regemorter Victoria; Mourad Michel; Lengele Benoit; Daumerie Chantal; Marbaix Etienne; Brichard Sonia; Many Marie Christine^*; Craps Julie

来源：Thyroid, 2016, 26(9): 1320-1331.

DOI：10.1089/thy.2015.0625

Background: Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a transcription 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), thyroperoxidase (TPO), and dual oxidase (DUOX), involved in extracellular iodination, is modulated by Th1 cytokines in human normal thyroid cells and in Hashimoto's thyroiditis (HT).
Objectives: The objectives of this study were (i) to analyze the PPAR gamma protein and mRNA expression at the follicular level in HT versus controls in correlation with the one of Cav-1; (ii) to study the effects of Th1 cytokines on PPAR gamma and catalase expression in human thyrocyte primary cultures; and (iii) to study the effects of pioglitazone, a PPAR gamma agonist, on thyroxisome components (Cav-1, TPO, DUOX) and on catalase, involved in antioxidant defense.
Results: Although the global expression of PPAR gamma in the whole gland of patients with HT was not modified compared with controls, there was great heterogeneity among glands and among follicles within the same thyroid. Besides normal (type 1) follicles, there were around inflammatory zones, hyperactive (type 2) follicles with high PPAR gamma and Cav-1 expression, and inactive (type 3) follicles which were unable to form thyroxine and did not express PPAR gamma or Cav-1. In human thyrocytes in primary culture, Th1 cytokines decreased PPAR gamma and catalase expression; pioglitazone increased Cav-1, TPO, and catalase expression.
Conclusion: PPAR gamma may play a central role in normal thyroid physiology by upregulating Cav-1, essential for the organization of the thyroxisome and extracellular iodination. By upregulating catalase, PPAR gamma may also contribute to cell homeostasis. The inhibitory effect of Th1 cytokines on PPAR gamma expression may be considered as a new pathogenetic mechanism for HT, and the use of PPAR gamma agonists could open a new therapeutic approach.

• 出版日期2016-9