Excessive Iodine Induces Thyroid Follicular Epithelial Cells Apoptosis by Activating HIF-1α-mediated Hypoxia Pathway in Hashimoto Thyroiditis

Purpose: Hashimoto thyroiditis (HT) is considered the most common autoimmune thyroid disease. A growing body of evidence suggests that HT incidence correlates with excessive iodine intake. We should probe the effects of excessive iodine intake in HT development and its possible mechanism. Methods: The study recruited 20 patients: 10 with HT and 10 with nodular goiter. We detected the expression of an apoptosis-related protein caspase-3 by immunohistochemistry. In vitro study, we explored the proliferation and apoptosis status in thyroid follicular cells (TFCs) stimulated at different iodine concentrations by MTT and flow cytometry. Then we performed RNA sequence analysis of Nthy-ori3-1 cells treated for 48h with different KI concentrations to probe the underlying mechanism. Finally, we used RT-PCR to verify its results. Results: We identified apoptosis in thyroid tissue obtained from HT patients coincides with the increase of caspase-3 levels. In vitro study, iodine suppressed proliferation of TFCs and promoted TFCs apoptosis in a dose-dependent manner. RNA sequence results showed that high concentration of iodine activate the hypoxia-inducible factor-1α (HIF-1α)-mediated hypoxia pathway coincide with the upregulation of N-myc downregulated gene-1 (NDRG1) expression. Conclusions: Our study confirmed that excessive iodine adsorption activates the HIF-1α-mediated hypoxia pathway to promote apoptosis of TFCs, which may be an important risk factor contributing to HT development.