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Department of Pediatric Cardiology, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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B lymphocytes are the source of autoantibodies against the thyroid-stimulating hormone receptor (TSHR) in Graves’ disease (GD). Characterization of autoimmune B-cell expression profiles might enable a better understanding of GD pathogenesis. To reveal this, the expression levels of long noncoding RNAs (lncRNAs) and mRNAs (genes) in purified B cells from patients with newly diagnosed GD and healthy individuals were compared using microarrays, which elucidated 604 differentially expressed lncRNAs (DE-lncRNAs) and 410 differentially expressed genes (DEGs). GO and pathway analyses revealed that the DEGs are mainly involved in immune response. A protein–protein interaction network presented experimentally validated interactions among the DEGs. Two independent algorithms were used to identify the DE-lncRNAs that regulate the DEGs. Functional annotation of the deregulated lncRNA–mRNA pairs identified 14 pairs with mRNAs involved in cell proliferation. The lncRNAs TCONS_00022357-XLOC_010919 and n335641 were predicted to regulate TCL1 family AKT coactivator A (TCL1A), and the lncRNA n337845 was predicted to regulate SH2 domain containing 1A (SH2D1A). TCL1A and SH2D1A are highly involved in B-cell proliferation. The differential expression of both genes was validated by qRT-PCR. In conclusion, lncRNA and mRNA expression profiles of B cells from patients with GD indicated that the lncRNA–mRNA pairs n335641–TCL1A, TCONS_00022357-XLOC_010919–TCL1A, and n337845–SH2D1A may participate in GD pathogenesis by modulating B-cell proliferation and survival. Therefore, the identified lncRNA and mRNA may represent novel biomarkers and therapeutic targets for GD.
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Objective
To explore the relationship between estradiol (E2) and thyroid function during the second trimester of pregnancy and the effect of E2 on sodium iodide transporter (NIS) expression in cultured thyroid cells.
Materials and methods
We analyzed relationships between E2 and thyroid function in 196 pregnant women during the second trimester. Multiple linear regression analysis was performed between E2 and thyroid function. The human thyroid Nthy-ori3-1 cells were cultured in different E2 concentrations, and the mRNA levels of NIS, estrogen receptor (ER)-α, and ER-β were measured by quantitative real-time PCR. Their protein levels were assessed by western blot.
Results
E2 was positively correlated with thyroid-stimulating hormone (TSH) and negatively correlated with free thyroxine (FT4) (P < 0.05). When we corrected for age, BMI, alanine aminotransferase, and serum creatinine, E2 was still negatively correlated with FT4 (P < 0.5) during the second trimester. In Nthy-ori3-1 cells treated with 10 nM E2, NIS and ER-β mRNA levels were significantly reduced, while ER-α mRNA level was not altered (P > 0.5). Moreover, 10 nM E2 significantly decreased protein levels of ER-β, phosphorylated versions of protein kinase A (p-PKA), phosphorylated versions of cAMP response element-binding protein (p-CREB), and NIS, while treatment with the ER-β inhibitor restored the expression of p-PKA, p-CREB, and NIS (P < 0.05).
Conclusion
High concentration of E2 has a negative correlation with FT4. High concentration of E2 can inhibit the NIS expression through the ER-β-mediated pathway, which may cause thyroid hormone fluctuations during pregnancy.
