Dysregulated Vitamin D Signaling in Hashimoto's Thyroiditis: An Integrated Transcriptomic Study in a Korean Cohort

Dong-Woo Lim¹Ho-Jung Jeong²Jin Seok Lee²Min-Seo Choi^3,4Sungsoon Fang^4,5Jing- Hua Wang⁶Hojun Kim⁶Seok-Mo Kim^7*

• ¹College of Korean Medicine, Dongguk University, Gyeongju, Republic of Korea
• ²Ajou University School of Medicine, Suwon-si, Republic of Korea
• ³Yonsei University Brain Korea 21 Project for Medical Science, Seodaemun-gu, Republic of Korea
• ⁴Department of Biomedical Sciences, Yonsei University Seoul, Republic of Korea, Seoul, Republic of Korea
• ⁵Yonsei University Brain Korea 21 Project for Medical Science, Seoul, Republic of Korea
• ⁶Department of Rehabilitation Medicine, College of Korean Medicine, Dongguk University, Goyang, Republic of Korea, Goyang, Republic of Korea
• ⁷Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea, Seoul, Republic of Korea

Background: Hashimoto's thyroiditis (HT) is the most common thyroid disease leading to hypothyroidism in developed countries. Recent studies have highlighted vitamin D as a potential risk factor or therapeutic agent for HT owing to its role in modulating immune responses, although concrete evidence has not been presented. This retrospective observational study was conducted to investigate serum vitamin D levels and dysregulation of vitamin D signaling pathways in patients with HT. Methods: Patients who underwent thyroid surgery for various thyroid neoplasm with or without HT were recruited. We analyzed serum thyroid biomarkers, including serum vitamin D, anti-thyroglobulin (TG) antibody, and anti-thyroid peroxidase (TPO) antibody for patients with HT. Using RNA-seq, the gene expression profile of thyroid tissue and the potential correlation between HT and vitamin D levels or its signaling were investigated. Results: The serum vitamin D levels were significantly lower in patients with HT. However, vitamin D receptor (VDR) expression and genes involved in vitamin D-associated biological process (BP) were significantly upregulated in the HT group. Visualization of expression profile on Wikipathways revealed multifaceted regulation of vitamin D-related pathways in the HT group. Real-time PCR and immunofluorescence staining confirmed enhanced VDR expression in thyroid tissues from the HT cohort. Conclusion: Our study presents the first RNA-seq dataset obtained acquired from a the Korean HT cohort in this study, and highlighted dysregulated vitamin D signaling in thyroid tissues from the HT cohort. Further investigations are needed to elucidate the causal role of vitamin D signaling in the pathogenesis of HT.