期刊
BIOMEDICINES
卷 9, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines9101471
关键词
systemic sclerosis; pathogenesis; epigenetic mechanisms; miRNAs
资金
- Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca [2461/64/17, 4335/01.10.2018, 1033/57/13]
Systemic sclerosis (SSc) is a rare connective tissue disease with heterogeneous clinical phenotypes characterized by microangiopathy, immune dysfunction, and fibrosis. Epigenetic mechanisms and miRNAs play crucial roles in SSc pathogenesis, offering potential as biomarkers and therapeutic targets.
Systemic sclerosis (SSc) is a rare connective tissue disease with heterogeneous clinical phenotypes. It is characterized by the pathogenic triad: microangiopathy, immune dysfunction, and fibrosis. Epigenetic mechanisms modulate gene expression without interfering with the DNA sequence. Epigenetic marks may be reversible and their differential response to external stimuli could explain the protean clinical manifestations of SSc while offering the opportunity of targeted drug development. Small, non-coding RNA sequences (miRNAs) have demonstrated complex interactions between vasculature, immune activation, and extracellular matrices. Distinct miRNA profiles were identified in SSc skin specimens and blood samples containing a wide variety of dysregulated miRNAs. Their target genes are mainly involved in profibrotic pathways, but new lines of evidence also confirm their participation in impaired angiogenesis and aberrant immune responses. Research approaches focusing on earlier stages of the disease and on differential miRNA expression in various tissues could bring novel insights into SSc pathogenesis and validate the clinical utility of miRNAs as biomarkers and therapeutic targets.
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