Irrespective of Plaque Activity, Multiple Sclerosis Brain Periplaques Exhibit Alterations of Myelin Genes and a TGF-Beta Signature
Abstract
:1. Introduction
2. Results
2.1. Irrespective of Plaque Activity, the Myelin-Related Genes MAG, NDRG1, OLIG1 and OLIG2 Exhibit Decreased Expression Levels in Periplaques
2.2. TGFB2 and a Specific Set of Genes Coding for Cytokines/Chemokines or Growth Factors Are Over-Expressed in Periplaques
2.3. Irrespective of Plaque Activity, a Significant Number of Genes Upregulated in Periplaques Are Involved in the TGF-Beta Receptor Signaling Pathway
- Signaling by TGF-beta receptor complex;
- EGF/EGFR signaling pathway;
- Signaling events mediated by hepatocyte growth factor receptor (c-Met);
- Angiopoietin receptor Tie2-mediated signaling.
2.4. Silent Periplaques Exhibit a Genomic Signature Linking TGFB2 to the NDRG1-Silencing Molecule MYCN
2.5. NDRG1 Interacts with mRNA-Binding Proteins Involved in the Post-Transcriptional Regulation of Myelin Genes
3. Discussion
4. Materials and Methods
4.1. Bioinformatics Analyses of Genomics Data
4.2. Bioinformatics Analyses of Proteomics Data
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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MAG | OLIG1 | OLIG2 | NDRG1 | |
---|---|---|---|---|
TGFB2 | p = 0.0028 r = −0.58 | p = 0.00069 r = −0.64 | p = 0.00016 r = −0.69 | p = 0.0042 r = −0.55 |
ANGPT1 | NS | NS | p = 0.0039 r = −0.56 | 0.021 r = 0.46 |
EGF | p = 0.027 r = −0.44 | p = 0.044 r = −0.40 | p = 0.00055 r = −0.65 | p = 0.0010 r = −0.62 |
HGF | p = 0.00058 r = −0.65 | p = 0.00032 r = −0.67 | p = 0.0000086 r = −0.77 | p = 0.000010 r = −0.77 |
IL15 | NS | NS | 0.00027 r = −0.67 | 0.013 r = −0.49 |
Pathway | Localization | ||
---|---|---|---|
Rims of CA plaques | Active periplaques | Silent periplaques | |
Signaling by TGF-beta receptor complex | 0.015 | 0.010 | 9.5 × 10−4 |
EGF/EGFR signaling pathway | 0.0038 | NS | 0.0030 |
Signaling events mediated by hepatocyte growth factor receptor (c-Met) | NS | NS | 0.012 |
Angiopoietin receptor Tie2-mediated signaling | NS | NS | NS |
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Nataf, S.; Guillen, M.; Pays, L. Irrespective of Plaque Activity, Multiple Sclerosis Brain Periplaques Exhibit Alterations of Myelin Genes and a TGF-Beta Signature. Int. J. Mol. Sci. 2022, 23, 14993. https://doi.org/10.3390/ijms232314993
Nataf S, Guillen M, Pays L. Irrespective of Plaque Activity, Multiple Sclerosis Brain Periplaques Exhibit Alterations of Myelin Genes and a TGF-Beta Signature. International Journal of Molecular Sciences. 2022; 23(23):14993. https://doi.org/10.3390/ijms232314993
Chicago/Turabian StyleNataf, Serge, Marine Guillen, and Laurent Pays. 2022. "Irrespective of Plaque Activity, Multiple Sclerosis Brain Periplaques Exhibit Alterations of Myelin Genes and a TGF-Beta Signature" International Journal of Molecular Sciences 23, no. 23: 14993. https://doi.org/10.3390/ijms232314993