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Dysregulation of Vitamin D and Its Signaling in Hashimoto's Thyroiditis in Korean Population

ABSTRACT: Hahimoto’s thyroiditis (HT) is the most common thyroid disease leads to hypothyroid in developed countries. Recent studies highlighted the Vitamin D as the potential risk factor or the therapeutic agents for the HT due to its role in modulating immune responses, while the concrete evidence has not been presented. Patients eligible for the surgery of papillary thyroid cancer (PTC) with or without HT were recruited for the study. We analyzed serum thyroid biomarkers including serum vitamin D, anti-TG, anti-TPO for HT patients. Using the RNA-seq the gene expression profile of thyroid tissue, potential correlation between HT and vitamin D or its signaling was investigated. HT cohort showed common clinical characteristics known for the HT in serum biomarkers and enrichment analysis of BP terms and KEGG pathways. Serum vitamin D level was significantly lower in HT patients. However, vitamin D receptor (VDR) expression and genes involved in vitamin D-associated BP terms were significantly upregulated in HT. Real-time PCR and Immunofluorescence staining confirmed enhanced VDR expression throughout the thyroid tissue of HT cohort. This study demonstrated dysregulated vitamin D signaling in thyroid tissue of HT cohort. Further study need to be performed to elucidate etiology, susceptibility, and development of HT in relation with vitamin D signaling.

ORGANISM(S): Homo sapiens

PROVIDER: GSE286332 | GEO | 2025/09/01

REPOSITORIES: GEO

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Project description:Objectives: Hashimoto’s thyroiditis (HT) is one of the most common autoimmune disorders; however, its underlying pathological mechanisms remain unclear. Although aberrant glycosylation has been implicated in the N-glycome of immunoglobulin G (IgG), changes in serum proteins have not been comprehensively characterized. This study aimed to investigate the glycosylation profile of serum samples of HT patients that were depleted of highly abundant proteins by and propose the potential functions of glycoproteins for the further study of pathological mechanisms of HT . Methods: A lectin microarray containing 70 lectins was used to detect and analyze glycosylation of serum proteins using serum samples (N=27 HT; N=26 healthy control [HC]) depleted of abundant proteins. Significant differences in glycosylation status between HT patients and the HC group were verified by lectin blot analysis. A lectin-based pull-down assay combined with mass spectrometry was used to investigate potential glycoproteins combined with differentially present lectins, and an enzyme-linked immunosorbent assay (ELISA) was used to identify the expression of targeted glycoproteins in 131 patients with papillary thyroid carcinoma (PTC), 131 patients with benign thyroid nodules (BTN) patients, 130 patients with HT, and 128 HCs. Results: Compared with the HC group, the majority of the lectin binding signals in HT group were weakened, while the Vicia villosa agglutinin (VVA) binding signal was increased. The difference in VVA binding signals verified by lectin blotting was consistent with the results of the lectin microarray. A total of 113 potential VVA-binding glycoproteins were identified by mass spectrometry and classified by gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses . Using ELISA, we confirmed that lactoferrin (LTF) and mannan-binding lectin-associated serine protease 1 (MASP-1) levels were elevated in the serum of patients with HT and PTC. Conclusions: Following depletion of abundant proteins, remaining serum proteins in HT patients exhibited lower glycosylation levels than those observed in HCs. An increased level of potential VVA-binding glycoproteins may play an important role in HT development. LTF and MASP-1 expression was significantly higher in the serum of HT and PTC patients, suggesting key roles played by glycosylation in pathological mechanisms underlying HT and PTC.

Project description:PURPOSE: Amino acids (AAs) play important physiological roles in living cells. Some amino acid changes in blood are specific for autoimmune disorders, and some are specific for thyroid cancer. The aims of this study were to profile AA metabolites in the serum of patients with papillary thyroid carcinoma (PTC0) without Hashimoto’s thyroiditis (HT) and patients with PTC with HT (PTC1) and predict whether AA metabolites are associated with thyroid disease, thyroid hormone and thyroid autoantibodies. METHODS: A total of 93 serum samples were collected, including 28 healthy controls (HCs), 28 PTC0 patients and 37 PTC1 patients. Serum samples were analysed by high-performance liquid chromatography-triple stage quadrupole-mass spectrometry (HPLC-TSQ-MS), and 21 amino acids (AAs) were detected.RESULTS: The serum concentration of glutamic acid was significantly elevated in PTC1 patients compared with PTC0 patients. Lysine was the second amino acid that differentiated these two groups of PTC patients. In addition, the serum concentrations of glycine, alanine and tyrosine were significantly reduced in both PTC patient groups compared to the HC group. These AAs were also correlated with thyroid hormones and antibodies. Five amino acid markers, namely, glycine, tyrosine, glutamic acid, glutamine and arginine, separated/distinguished PTC0 patients from healthy subjects, and eight AA markers, the same AAs as above without arginine but with alanine, leucine, valine and histidine, separated/distinguished PTC1 patients from healthy subjects based on ROC analysis.CONCLUSION: Compared with the HCs, changes in AAs in PTC0 and PTC1 patients showed similar patterns, suggesting the possibility of a common pathophysiological basis, which confirms preliminary research that PTC is significantly associated with pathologically confirmed HT. We found two AAs, lysine and alanine, that can perform diagnostic functions in distinguishing PTC1 from PTC0.

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Dysregulation of Vitamin D and Its Signaling in Hashimoto's Thyroiditis in Korean Population

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