ArticleAnnals of the rheumatic diseases2018
Scleroderma fibroblasts suppress angiogenesis via TGF-β/caveolin-1 dependent secretion of pigment epithelium-derived factor.
Article in Annals of the rheumatic diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Aurora A kinase activation contributes to the fibrotic phenotype in systemic sclerosis through primary cilia shortening.Arthritis research & therapy · 2026Article
- Revolutionizing Autoimmune Research: The Role of Caveolin-1.Immunity, inflammation and disease · 2025Review
- PEDF and Its Role in Metabolic Disease, Angiogenesis, Cardiovascular Disease, and Diabetes.Biomedicines · 2025Review
- Biological hallmarks of systemic sclerosis are present in the skin and serum of patients with Very Early Diagnosis of Systemic Sclerosis (VEDOSS).Rheumatology (Oxford, England) · 2025Article
- Acute Stress and Autoimmune Markers: Evaluating the Psychoneuroimmunology Axis in Firefighter Recruits.International journal of molecular sciences · 2025Article
- Serum Proteomic Markers in Patients with Systemic Sclerosis in Relation to Silica Exposure.Journal of clinical medicine · 2025Article
- Systemic Sclerosis Dermal Fibroblast Exosomes Trigger Type 1 Interferon Responses in Keratinocytes via a TBK/JAK/STAT Signaling Axis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Association of serum Ly6/PLAUR domain-containing protein 1 levels with skin sclerosis in systemic sclerosis.Scientific reports · 2024Article
- Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis.Biomedicines · 2023Article
- PEDF Protects Endothelial Barrier Integrity during Acute Myocardial Infarction via 67LR.International journal of molecular sciences · 2023Article
- Integrated single-cell RNA-seq analysis reveals the vital cell types and dynamic development signature of atherosclerosis.Frontiers in physiology · 2023Article
- Novel role of long non-coding RNAs in autoimmune cutaneous disease.Journal of cell communication and signaling · 2022Review
- Involvement of caveolin-1 in skin diseases.Frontiers in immunology · 2022Review
- 1α,25-Dihydroxyvitamin D3 Promotes Angiogenesis After Cerebral Ischemia Injury in Rats by Upregulating the TGF-β/Smad2/3 Signaling Pathway.Frontiers in cardiovascular medicine · 2022Article
- Downregulation of Vascular Hemeoxygenase-1 Leads to Vasculopathy in Systemic Sclerosis.Frontiers in physiology · 2022Article
- Interrelationship and Sequencing of Interleukins4, 13, 31, and 33 - An Integrated Systematic Review: Dermatological and Multidisciplinary Perspectives.Journal of inflammation research · 2022Review
- Engineering Advanced In Vitro Models of Systemic Sclerosis for Drug Discovery and Development.Advanced biology · 2021Review
- Dynamics of digital ulcers in systemic sclerosis.Experimental and therapeutic medicine · 2020Article
- Long non-coding RNA HOTAIR drives EZH2-dependent myofibroblast activation in systemic sclerosis through miRNA 34a-dependent activation of NOTCH.Annals of the rheumatic diseases · 2020Article
- The importance of caveolins and caveolae to dermatology: Lessons from the caves and beyond.Experimental dermatology · 2020Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
objectivesSystemic sclerosis (SSc) is characterised by tissue fibrosis and vasculopathy with defective angiogenesis. Transforming growth factor beta (TGF-β) plays a major role in tissue fibrosis, including downregulation of caveolin-1 (Cav-1); however, its role in defective angiogenesis is less clear. Pigment epithelium-derived factor (PEDF), a major antiangiogenic factor, is abundantly secreted by SSc fibroblasts. Here, we investigated the effect of TGF-β and Cav-1 on PEDF expression and the role of PEDF in the ability of SSc fibroblasts to modulate angiogenesis.
methodsPEDF and Cav-1 expression in fibroblasts and endothelial cells were evaluated by means of immunohistochemistry on human and mouse skin biopsies. PEDF and Cav-1 were silenced in cultured SSc and control fibroblasts using lentiviral short-hairpin RNAs. Organotypic fibroblast-endothelial cell co-cultures and matrigel assays were employed to assess angiogenesis.
resultsPEDF is highly expressed in myofibroblasts and reticular fibroblasts with low Cav-1 expression in SSc skin biopsies, and it is induced by TGF-β in vitro. SSc fibroblasts suppress angiogenesis in an organotypic model. This model is reproduced by silencing Cav-1 in normal dermal fibroblasts. Conversely, silencing PEDF in SSc fibroblasts rescues their antiangiogenic phenotype. Consistently, transgenic mice with TGF-β receptor hyperactivation show lower Cav-1 and higher PEDF expression levels in skin biopsies accompanied by reduced blood vessel density.
conclusionsOur data reveal a new pathway by which TGF-β suppresses angiogenesis in SSc, through decreased fibroblast Cav-1 expression and subsequent PEDF secretion. This pathway may present a promising target for new therapeutic interventions in SSc.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.