Autor: |
Qian Yang, Qinnan Zhang, Fanfan Pan, Bingbing Zha |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
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Zdroj: |
Endocrine Connections, Vol 13, Iss 12, Pp 1-8 (2024) |
Druh dokumentu: |
article |
ISSN: |
2049-3614 |
DOI: |
10.1530/EC-24-0428 |
Popis: |
Background: Signal transducer and activator of transcription 6 (STAT6) is an important nuclear transcription factor. Previous studies demonstrated that blocking STAT6 can ameliorate thyroid function by reducing serum T3 and T4. Sodium/iodide symporter (NIS) is a key protein that mediates active iodine uptake and plays an important role in regulating thyroid function. This study explored the interaction between STAT6 and NIS. Methods: Immunohistochemical staining was performed for detecting the expression of NIS in different tissues. RT-PCR was performed for evaluating the mRNA level of NIS when Nthy-ori 3-1 cells were incubated with IL4, thyroid stimulating hormone (TSH), or monoclonal thyroid-specific stimulatory autoantibody (TSAb) for 24 h. Quantitative RT-PCR, western blot, and immunofluorescence analysis were performed for detecting NIS expression after inhibiting STAT6 phosphorylation by AS1517499. Finally, we used luciferase reporter assays to explore the ability of STAT6 to regulate the promoter activity of the NIS-coding gene. Results: NIS was highly expressed in thyroid epithelial cells of EAGD mice or Graves’ disease (GD) patients, and TSAb increased the expression of NIS. We show that a STAT6 phosphorylation inhibitor can attenuate the effect of TSAb on increasing NIS protein and mRNA levels. Finally, we confirm that transcription factor STAT6 can mediate NIS transcription and co-activator P100 protein can enhance STAT6-dependent transcriptional activation. Conclusion: In GD, TSAb induces STAT6 signaling to upregulate NIS expression, and STAT6 blockade ameliorates thyroid function via downregulation of the NIS. Our study furthers understanding of the effects of STAT6 on thyroid function and reveals new avenues for GD treatment. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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