Systemic sclerosis (SSc) is a prototypic fibrotic disease characterized by localized or diffuse skin thickening and fibrosis. Tissue fibrosis is driven by myofibroblasts, and factors affecting myofibroblast activation may also be involved in the development of SSc. In this study, we examined molecular mechanisms underlying SSc by focusing on myofibroblast activation processes. Bioinformatics analysis conducted to identify differentially expressed miRNAs (DEMs) and genes (DEGs) revealed that microRNA-16-5p (miR-16-5p) was downregulated and NOTCH2 was upregulated in SSc patients. In vitro experiments confirmed that miR-16-5p was able to bind directly to NOTCH2 and inhibit myofibroblast activation. Moreover, miR-16-5p-dependent inhibition of NOTCH2 decreased collagen and α-SMA expression. MiR-16-5p downregulation and NOTCH2 upregulation was also confirmed in vivo in SSc patients, and NOTCH2 activation promoted fibrosis progression in vitro . These results indicate that miR-16-5p suppresses myofibroblast activation by suppressing NOTCH signaling.
Purpose Resveratrol (Res) is a natural polyphenolic compound found in several plants and reported as a promising biological molecule with effective anti-fibrosis and anti-inflammatory activities. However, the underlying mechanism of Res on systemic sclerosis (SSc) remains unclear. In the study, we identified the key cellular signaling pathways involved in the Res regulatory process on SSc. Methods Res-targeted genes interaction network was constructed using the STITCH database, and the shared Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in both SSc and Res-targeted genes were then identified. The top five enriched KEGG pathways were visualized by GOplot. KEGG pathways associated with Res-targeted genes were established by Pathway Builder Tool 2.0. Quantitative real-time PCR (qRT-PCR) was used to assess the expression of sirtuin 1 (SIRT1), mammalian targeted of rapamycin (mTOR), and cytokines. Results Enrichment analysis of Res-targeted genes showed 79 associated pathways, 27 of which were also involved in SSc. Particularly, SIRT1/mTOR signaling was found as one of the crucial regulatory pathways. In vitro results suggested that SIRT1-mediated mTOR degradation ameliorated bleomycin (BLM)-induced fibrosis and inflammation. Res was capable of elevating the SIRT1 level in fibroblasts and partially reversing mTOR-dependent induction of fibrosis and inflammation. Conclusion These results indicated that Res is a feasible and effective choice for SSc and therapeutic target of mTOR could be a potential alternative for treatment of SSc.
Liu et al.: Cytochrome P450 27B1 Gene Polymorphism in Patients with Systemic Lupus Erythematosus Systemic lupus erythematosus is a severe inflammatory connective tissue disease induced by autoimmunity. The cytochrome p450 27B1 gene, activating Vitamin D precursor 25-hydroxyvitamin D into 1,25-dihydroxyvitamin D in immunity cells resulted in autoimmune disorders. This study was assessing the correlation and clinical pathological characteristics relationship between the cytochrome p450 27B1 gene polymorphism rs10877012/rs4646536 and systemic lupus erythematosus to provide a rationale for determining the role that cytochrome p450 27B1 gene polymorphism plays in systemic lupus erythematosus. In this study, we investigated the association of rs10877012 (T/G) polymorphism with systemic lupus erythematosus susceptibility in 156 patients with systemic lupus erythematosus compared to 156 healthy population, both groups came from the same Mendelian population by conformity to Hardy Weinberg equilibrium. DNA was extracted from peripheral leukocytes and analyzed for the polymorphism using the polymerase chain reaction-ligase detection reaction method. We found an association between the presence of the T allele at the polymorphic site (odds ratio=2.94; 95 % confidence interval 1.77-4.86; <0.0001) and a decreased colorectal cancer incidence. rs10877012 polymorphism was associated with arthritis and positive Anti-double stranded DNA antibody and increased C-reactive protein happened in patients with systemic lupus erythematosus.
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