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| Status |
Public on Jan 15, 2025 |
| Title |
Epigenetic changes cause aberrantly high expression of SOX11 leading to systemic sclerosis |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Systemic sclerosis (SSc) is a chronic, heterogenous multisystem connective tissue disease characterized by vascular injury, autoimmunity, and organ fibrosis. Epigenetic modification is thought to be important in the onset and progression of SSc. SOX (SRY-related HMG box) 11 is a transcription factor playing several important roles in organ development in embryos. We have previously shown that dermal fibroblasts derived from SSc patients showed constitutive, high expression of SOX11 and a positive loop formed by SOX11 and periostin in fibroblasts upregulates the TGF- signals, leading to skin fibrosis. However, the mechanism of the aberrant high expression of SOX11 remain unknown in the pathogenesis of SSc. In this study, we found that SOX11 high expression is associated with presence of activating histone marks (H3K27Ac) in SSc dermal fibroblasts. In contrast, normal fibroblasts express low level of SOX11 associated with silencing histone marks H3K27me3. Moreover, using the miRNA microarray method, we identified some miRNAs downregulated in SSc dermal fibroblasts and target SOX11 and overexpression of these miRNAs significantly repressed the expression of SOX11 in SSc dermal fibroblasts. Our findings, taken together, show that epigenetic activation of SOX11 in systemic sclerosis fibroblasts upregulates the SOX11 expression, leading to skin fibrosis.
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| Overall design |
We searched miRNAs differently expressed in normal and SSc dermal fibroblasts using microarray analysis and selected downregulated miRNAs in SSc dermal fibroblasts because miRNAs targeting the SOX11 gene are expected to downregulate its expression.
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| Contributor(s) |
Nanri Y, Izuhara K |
| Citation missing |
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| |
| Submission date |
May 31, 2024 |
| Last update date |
Jan 16, 2025 |
| Contact name |
Yasuhiro Nanri |
| E-mail(s) |
sp9710@cc.saga-u.ac.jp
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| Phone |
+81-952-34-2261
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| Organization name |
Saga Medical School
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| Department |
Department of Biomolecular Sciences
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| Street address |
5-1-1 Nabeshima
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| City |
Saga |
| ZIP/Postal code |
849-8501 |
| Country |
Japan |
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| Platforms (1) |
| GPL25134 |
Agilent-070156 Human_miRNA_V21.0_Microarray 046064 (miRNA ID version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA1118702 |
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