ArticleArthritis & rheumatology (Hoboken, N.J.)2019
Identification of Cysteine-Rich Angiogenic Inducer 61 as a Potential Antifibrotic and Proangiogenic Mediator in Scleroderma.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Metab8D: a metabolic regulome network from multiomics and machine learning.Communications biology · 2026Article
- A potent inhibitor of PAI-1, MDI-2517, mitigates disease severity in a preclinical systemic sclerosis model.JCI insight · 2026Article
- Androgen dysregulates the follicular extracellular matrix and increases pro-fibrotic gene expression in the mouse ovary.Scientific reports · 2026Article
- Review
- Role of 3-mercaptopyruvate sulfurtransferase in cancer: Molecular mechanisms and therapeutic perspectives.Translational oncology · 2025Review
- Cysteine-rich 61 inhibition attenuates hepatic insulin resistance and improves lipid metabolism in high-fat diet fed mice and HepG2 cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Noval advance of histone modification in inflammatory skin diseases and related treatment methods.Frontiers in immunology · 2023Review
- SARA suppresses myofibroblast precursor transdifferentiation in fibrogenesis in a mouse model of scleroderma.JCI insight · 2022Article
- HDAC5 inactivates CYR61-regulated CD31/mTOR axis to prevent the occurrence of preeclampsia.Cell and tissue research · 2022Article
- Inhibition of bromodomain extraterminal histone readers alleviates skin fibrosis in experimental models of scleroderma.JCI insight · 2022Article
- Natural Bioactive Compounds Targeting Histone Deacetylases in Human Cancers: Recent Updates.Molecules (Basel, Switzerland) · 2022Review
- Functional Characterization of Glycoprotein Nonmetastatic Melanoma Protein B in Scleroderma Fibrosis.Frontiers in immunology · 2022Article
- Expression of Cyr61 is associated with clinical course in patients with Crohn's disease.BMC gastroenterology · 2021Article
- Characterization of Histone Deacetylase Mechanisms in Cancer Development.Frontiers in oncology · 2021Review
- Emerging Roles of Matricellular Proteins in Systemic Sclerosis.International journal of molecular sciences · 2020Review
- Epigenetic Control of Scleroderma: Current Knowledge and Future Perspectives.Current rheumatology reports · 2019Review
- CCN1 expression by fibroblasts is required for bleomycin-induced skin fibrosis.Matrix biology plus · 2019Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveWe previously identified CYR61 as a histone deacetylase 5 (HDAC-5)-repressed gene in systemic sclerosis (SSc; scleroderma) endothelial cells (ECs). When overexpressed, cysteine-rich angiogenic inducer 61 (CYR-61) promoted angiogenesis in SSc ECs. This study was undertaken to examine the role of CYR-61 in fibrosis and determine the mechanisms involved in CYR-61-mediated angiogenesis in SSc.
methodsDermal ECs and fibroblasts were isolated from biopsy specimens from healthy subjects and patients with SSc. CYR-61 level was determined by quantitative polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. CYR-61 was overexpressed using a CYR61 vector or knocked down using small interfering RNA, and functional and mechanistic studies were then conducted in fibroblasts and ECs.
resultsLower CYR61 messenger RNA levels were observed in dermal fibroblasts and ECs from SSc patients than in those from healthy controls. In SSc fibroblasts, overexpression of CYR-61 led to significant reduction in the expression of profibrotic genes, including COL1A1 (P = 0.002) and ACTA2 (P = 0.04), and an increase in the expression of matrix-degrading genes, including MMP1 (P = 0.002) and MMP3 (P =0.004), and proangiogenic VEGF (P = 0.03). The antifibrotic effect of CYR-61 was further demonstrated by delay in wound healing, inhibition of gel contraction, inactivation of the transforming growth factor β pathway, and early superoxide production associated with senescence in SSc fibroblasts. In SSc ECs, overexpression of CYR-61 led to increased production of vascular endothelial cell growth factor. The proangiogenic effects of CYR-61 were mediated by signaling through αvβ3 receptors and downstream activation of AMP-activated protein kinase, AKT, and the endothelial cell nitric oxide synthase/nitric oxide pathway system.
conclusionCYR-61, which is epigenetically regulated by HDAC-5, is a potent antifibrotic and proangiogenic mediator in SSc. Therapeutic intervention to promote CYR-61 activity or increase CYR-61 levels might be of benefit in SSc.
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