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Published on: August 3, 2018
Alteration of circulating miRNAs in SSc: miR-30b regulates the expression of PDGF receptor β
Shigeru Tanaka1, Akira Suto, Kei Ikeda
1Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba City, Chiba 260-8670, Japan. suaki@faculty.chiba-u.jp.
Objective:
Although several miRNAs have been shown to regulate autoimmune pathogenesis by affecting lymphocyte function, the roles of miRNAs in the pathogenesis of SSc remain unclear. Therefore the purpose of this study was to identify miRNAs that play a role in the pathogenesis of SSc by quantitative PCR screening of serum miRNAs.
Methods:
Ninety-five miRNAs that were predicted to target SSc-related genes [IL-4, TGF-β, CTGF, PDGF-B, PDGF receptor (PDGFR) α/β and COL1A2) by in silico analyses were selected. The expression of these miRNAs in sera of SSc patients and healthy controls was measured by quantitative PCR. Involvement of miR-30b, which was most strongly down-regulated in SSc patients, in the regulation of PDGFR-β expression was examined by transfection experiments and 3'-untranslated region (3'-UTR) target luciferase assays. The expression of miR-30b in skin was evaluated in a bleomycin-induced dermal fibrosis model in mice and in SSc patients.
Results:
Nineteen of 95 miRNAs were significantly decreased in the sera of SSc patients. Among them, miR-30b was most strongly down-regulated in SSc patients (P = 0.00006) and the levels of miR-30b were inversely correlated with modified Rodnan skin scores. Transfection of a miR-30b mimic repressed PDGFR-β expression in dermal fibroblasts and the activity of a luciferase reporter containing 3'-UTR of PDGFR-β. Moreover, the expression of miR-30b was down-regulated in bleomycin-treated sclerotic skin and in affected skin in SSc patients.
Conclusion:
Down-regulation of miR-30b might be involved in the pathogenesis of SSc.
Insights
MicroRNAs (miRNAs) play a role in systemic sclerosis (SSc) pathogenesis. This study identified miR-30b as significantly down-regulated in SSc patients, suggesting its involvement in the disease.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are known regulators of autoimmune diseases.
- The specific roles of miRNAs in the pathogenesis of systemic sclerosis (SSc) are not well understood.
- Identifying key miRNAs can provide insights into SSc mechanisms.
Purpose of the Study:
- To identify miRNAs involved in the pathogenesis of SSc.
- To screen serum miRNAs using quantitative PCR.
- To investigate the functional role of a specific down-regulated miRNA in SSc.
Main Methods:
- Selected 95 miRNAs predicted to target SSc-related genes.
- Measured miRNA expression in serum from SSc patients and healthy controls via quantitative PCR.
- Validated the role of miR-30b in regulating PDGFR-β expression using cell-based assays and in vivo models.
Main Results:
- Nineteen out of 95 screened miRNAs were significantly decreased in SSc patients' sera.
- miR-30b was the most significantly down-regulated miRNA in SSc patients and inversely correlated with skin scores.
- miR-30b down-regulation was observed in dermal fibroblasts and fibrotic skin in mouse models and SSc patients.
Conclusions:
- Down-regulation of miR-30b is potentially implicated in the pathogenesis of SSc.
- miR-30b may regulate PDGFR-β expression, a key factor in fibrosis.
- Further research into miR-30b's role could reveal therapeutic targets for SSc.
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