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Published on: June 16, 2020
MicroRNA expression abnormalities in limited cutaneous scleroderma and diffuse cutaneous scleroderma
Honglin Zhu1, Yisha Li, Shunlin Qu
1Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
Abstract:
Scleroderma (systemic sclerosis, SSc) is a complex autoimmune disease caused by progressive fibrotic replacement of normal tissue architecture, a progressive and ultimately fatal process that currently has no cure. Although dysregulation of microRNAs (miRNAs) is known to be involved in a variety of pathophysiologic processes, the role of miRNAs in SSc is unclear. In comparison with the normal skin tissues, miRNAs were aberrantly expressed in limited cutaneous scleroderma and diffuse cutaneous scleroderma skin tissues. We also identified miRNAs whose expressions were correlated with SSc fibrosis: miR-21, miR-31, miR-146, miR-503, miR-145, and miR-29b were predicted to be involved. This study further confirmed that miR-21 was increased whereas miR-145 and miR-29b were decreased both in the skin tissues and fibroblasts. As predicted target genes, SMAD7, SAMD3, and COL1A1 were regulated by these miRNAs. After stimulation with transforming growth factor β, the expression of miR-21 was increased and that of SMAD7 mRNA was decreased. MiR-145 was upregulated whereas the mRNA level of SMAD3 was downregulated. The downregulation of miR-29b was correlated with the upregulation of COL1A1 mRNA. MiRNAs might play an important role in the pathogenesis of SSc and suggest a potential therapy.
Insights
MicroRNAs (miRNAs) show altered expression in scleroderma (SSc) skin, impacting fibrosis. Specific miRNAs like miR-21, miR-145, and miR-29b regulate fibrotic genes, suggesting potential SSc therapeutic targets.
Area of Science:
- Biochemistry
- Immunology
- Genetics
Background:
- Scleroderma (systemic sclerosis, SSc) is a fatal autoimmune fibrotic disease with no cure.
- MicroRNA (miRNA) dysregulation is implicated in various diseases, but their role in SSc pathogenesis remains unclear.
Purpose of the Study:
- To investigate the expression patterns and functional roles of microRNAs (miRNAs) in scleroderma (SSc) skin tissues.
- To identify specific miRNAs and their target genes involved in SSc-associated fibrosis.
Main Methods:
- Comparative analysis of miRNA expression in normal, limited cutaneous SSc, and diffuse cutaneous SSc skin tissues.
- Correlation analysis of miRNA expression with SSc fibrosis.
- Validation of miRNA and target gene expression in skin tissues and fibroblasts.
- Investigating miRNA regulation of target genes (SMAD7, SMAD3, COL1A1) following TGF-β stimulation.
Main Results:
- Aberrant miRNA expression was observed in SSc skin tissues compared to normal controls.
- Specific miRNAs (miR-21, miR-31, miR-146, miR-503, miR-145, miR-29b) were correlated with SSc fibrosis.
- miR-21 was upregulated, while miR-145 and miR-29b were downregulated in SSc tissues and fibroblasts.
- These miRNAs regulated predicted target genes involved in fibrotic processes (SMAD7, SMAD3, COL1A1).
Conclusions:
- MicroRNAs play a significant role in the pathogenesis of scleroderma (SSc).
- The identified miRNAs and their regulatory pathways offer potential therapeutic targets for SSc treatment.
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