ArticlePloS one2013
Desmoglein-2-integrin Beta-8 interaction regulates actin assembly in endothelial cells: deregulation in systemic sclerosis.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Desmoglein-2 promotes the proliferation and invasion of lung adenocarcinoma cells by inhibiting anoikis through the activation of the integrin beta-1/focal adhesion kinase signaling pathway.American journal of cancer research · 2026Article
- Pathogenesis of systemic sclerosis: an integrative review of recent advances.Journal of rheumatic diseases · 2025Review
- Endothelial Dysfunction in Systemic Sclerosis.International journal of molecular sciences · 2023Review
- Desmoglein-2 as a cancer modulator: friend or foe?Frontiers in oncology · 2023Review
- Desmoglein-2 is important for islet function and β-cell survival.Cell death & disease · 2022Article
- Desmoglein-2 expression is an independent predictor of poor prognosis patients with multiple myeloma.Molecular oncology · 2022Article
- Rho GTPase signaling in rheumatic diseases.iScience · 2022Review
- Baicalein Inhibits Metastatic Phenotypes in Nasopharyngeal Carcinoma Cells via a Focal Adhesion Protein Integrin β8.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Article
- Arrhythmogenic Cardiomyopathy Is a Multicellular Disease Affecting Cardiac and Bone Marrow Mesenchymal Stromal Cells.Journal of clinical medicine · 2021Article
- Mechanisms of Mechanical Force Induced Pulmonary Vascular Endothelial Hyperpermeability.Frontiers in physiology · 2021Review
- Tomatine Displays Antitumor Potential in In Vitro Models of Metastatic Melanoma.International journal of molecular sciences · 2020Article
- Desmocollin-2 promotes intestinal mucosal repair by controlling integrin-dependent cell adhesion and migration.Molecular biology of the cell · 2020Article
- KC21 Peptide Inhibits Angiogenesis and Attenuates Hypoxia-Induced Retinopathy.Journal of cardiovascular translational research · 2019Article
- The Role of Fibrinolytic Regulators in Vascular Dysfunction of Systemic Sclerosis.International journal of molecular sciences · 2019Review
- Pulmonary Endothelial Mechanical Sensing and Signaling, a Story of Focal Adhesions and Integrins in Ventilator Induced Lung Injury.Frontiers in physiology · 2019Review
- Metabolic shift in density-dependent stem cell differentiation.Cell communication and signaling : CCS · 2017Article
- A non-canonical role for desmoglein-2 in endothelial cells: implications for neoangiogenesis.Angiogenesis · 2016Article
- Desmoglein 2 promotes vasculogenic mimicry in melanoma and is associated with poor clinical outcome.Oncotarget · 2016Article
- Activation of the Thromboxane A2 Receptor by 8-Isoprostane Inhibits the Pro-Angiogenic Effect of Vascular Endothelial Growth Factor in Scleroderma.The Journal of investigative dermatology · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe inability of endothelial cells of patients affected by the diffuse form of Systemic sclerosis (SSc) to perform angiogenesis is a marker of the disease. We previously demonstrated that desmoglein-2 reduction is a major difference between (SSc)-microvascular endothelial cells (MVECs) and normal (N)-MVECs. Here we investigated the role of desmoglein-2 in human N-MVECs and SSc-MVECs angiogenesis. METHODOLOGY/PRINCIPAL
findingsAngiogenesis was studied by Matrigel invasion, capillary morphogenesis in vitro and Matrigel plug assay in vivo. Gene profiling was studied by Affymetrix technology and signal transduction by Western blotting. Colocalization was validated by immunoprecipitation and confocal microscopy. SiRNAs were used to validate the roles of specific molecules. We observed that desmoglein-2 co-localizes with integrin-beta8 in N-MVECs. This complex is required to signal through Rac, FAK, SMAD1/5 and MAP-kinases, promoting an angiogenic program. Inhibition of desmoglein-2 by DSG2-siRNA impaired actin stress fibres formation, capillary morphogenesis in vitro and angiogenesis in vivo. Transcriptome profiling after DSG2 inhibition revealed alterations of several genes involved in actin organization. siRNA inhibition of integrin-beta8 and RAC2 also resulted into capillary morphogenesis impairment in N-MVECs, due to reduced expression of the same actin-assembly genes that were down-regulated by DSG2 silencing. SSc-MVECs showed down-regulation of the same genes in DSG2-siRNA treated N-MVECs, suggesting that impairment of desmoglein-2/integrin-beta8 complex contributes to angiogenesis derangement in SSc. Transfection of DSG2 in SSc-MVEC partially restored their angiogenic properties in vitro. CONCLUSIONS/SIGNIFICANCE: We have shown that impairment of actin assembly as a result of desmoglein-2/integrin-beta8 complex formation is a major factor contributing to angiogenesis deregulation in Systemic sclerosis.
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