Changes in the Expression of TGF-Beta Regulatory Pathway Genes Induced by Vitamin D in Patients with Relapsing-Remitting Multiple Sclerosis
Vitamin D is an environmental factor related to multiple sclerosis that plays a significant role in immune regulation. TGF-β is a superfamily of cytokines with an important dual effect on the immune system. TGF-β inhibits the Th1 response while facilitating the preservation of regulatory T cells (FO...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/19/14447 |
| Summary: | Vitamin D is an environmental factor related to multiple sclerosis that plays a significant role in immune regulation. TGF-β is a superfamily of cytokines with an important dual effect on the immune system. TGF-β inhibits the Th1 response while facilitating the preservation of regulatory T cells (FOXP3+) in an immunoregulatory capacity. However, when IL-6 is present, it stimulates the Th17 response. Our aim was to analyze the regulatory effect of vitamin D on the in vivo TGF-β signaling pathway in patients with relapsing-remitting multiple sclerosis (RRMS). A total of 21 patients with vitamin D levels < 30 ng/mL were recruited and supplemented with oral vitamin D. All patients were receiving disease-modifying therapy, with the majority being on natalizumab. Expression of <i>SMAD7</i>, <i>ERK1</i>, <i>ZMIZ1</i>, <i>BMP2</i>, <i>BMPRII</i>, <i>BMP4</i>, and <i>BMP5</i> was measured in CD4+ lymphocytes isolated from peripheral blood at baseline and one and six months after supplementation. <i>SMAD7</i> was overexpressed at six months with respect to baseline and month one. <i>ERK1</i> was overexpressed at six months with respect to month one of treatment. No significant differences in expression were observed for the remaining genes. No direct correlation was found with serum vitamin D levels. <i>BMPRII</i> expression changed differentially in non–natalizumab- versus natalizumab-treated patients. Changes were observed in the expression of <i>ERK1</i>, <i>BMP2</i>, and <i>BMP5</i> based on disease activity measured using the Rio-Score, <i>BMP2</i> in patients who had relapses, and <i>BMP5</i> in those whose EDSS worsened. Our results suggest indirect regulation of vitamin D in TGF-β pathway genes in patients with RRMS. |
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| ISSN: | 1661-6596 1422-0067 |