ArticleArthritis & rheumatology (Hoboken, N.J.)2015
Endothelin receptor blockade ameliorates vascular fragility in endothelial cell-specific Fli-1-knockout mice by increasing Fli-1 DNA binding ability.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2015. 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, 30 citations in OpenAlex.
- Pericytes mediate neuroinflammation via Fli-1 in endotoxemia and sepsis in mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- FLI1 in PBMCs contributes to elevated inflammation in combat-related posttraumatic stress disorder.Frontiers in psychiatry · 2024Article
- Suppression of Fli-1 protects against pericyte loss and cognitive deficits in Alzheimer's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Fli1 deficiency suppresses RALDH1 activity of dermal dendritic cells and related induction of regulatory T cells: a possible role in scleroderma.Arthritis research & therapy · 2021Article
- Altered Properties of Endothelial Cells and Mesenchymal Stem Cells Underlying the Development of Scleroderma-like Vasculopathy in KLF5Arthritis & rheumatology (Hoboken, N.J.) · 2020Article
- miR-145a Regulation of Pericyte Dysfunction in a Murine Model of Sepsis.The Journal of infectious diseases · 2020Article
- The role of the oncostatin M/OSM receptor β axis in activating dermal microvascular endothelial cells in systemic sclerosis.Arthritis research & therapy · 2020Article
- Active roles of dysfunctional vascular endothelium in fibrosis and cancer.Journal of biomedical science · 2019Review
- Cyclophosphamide Pulse Therapy Normalizes Vascular Abnormalities in a Mouse Model of Systemic Sclerosis Vasculopathy.The Journal of investigative dermatology · 2019Article
- Fli-1 transcription factor regulates the expression of caspase-1 in lung pericytes.Molecular immunology · 2019Article
- Fli-1 Governs Pericyte Dysfunction in a Murine Model of Sepsis.The Journal of infectious diseases · 2018Article
- Fli1-haploinsufficient dermal fibroblasts promote skin-localized transdifferentiation of Th2-like regulatory T cells.Arthritis research & therapy · 2018Article
- Vascular Leaking, a Pivotal and Early Pathogenetic Event in Systemic Sclerosis: Should the Door Be Closed?Frontiers in immunology · 2018Review
- Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma.The Journal of experimental medicine · 2017Article
- Glycyrrhizin Ameliorates Fibrosis, Vasculopathy, and Inflammation in Animal Models of Systemic Sclerosis.The Journal of investigative dermatology · 2017Article
- Discovery of Dual ETA/ETB Receptor Antagonists from Traditional Chinese Herbs through in Silico and in Vitro Screening.International journal of molecular sciences · 2016Article
- Vasculopathy in scleroderma.Seminars in immunopathology · 2015Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveIt is generally accepted that blockade of endothelin receptors has potentially beneficial effects on vasculopathy associated with systemic sclerosis (SSc). The aim of this study was to clarify the molecular mechanism underlying these effects using endothelial cell-specific Fli-1-knockout (Fli-1 ECKO) mice, an animal model of SSc vasculopathy.
methodsLevels of messenger RNA for target genes and the expression and phosphorylation levels of target proteins were determined in human and murine dermal microvascular endothelial cells by real-time quantitative reverse transcription-polymerase chain reaction and immunoblotting, respectively. The binding of Fli-1 to the target gene promoters was evaluated using chromatin immunoprecipitation. Expression levels of Fli-1 and α-smooth muscle actin in murine skin were evaluated using immunohistochemistry. Vascular structure and permeability were evaluated in mice injected with fluorescein isothiocyanate-dextran and Evans blue dye, respectively.
resultsIn human dermal microvascular endothelial cells, endothelin 1 induced phosphorylation of Fli-1 at Thr(312) through the sequential activation of c-Abl and protein kinase Cδ, leading to a decrease in Fli-1 protein levels as well as a decrease in binding of Fli-1 to the target gene promoters, whereas bosentan treatment reversed those effects. In Fli-1 ECKO mice, 4 weeks of treatment with bosentan increased endothelial Fli-1 expression, resulting in vascular stabilization and the restoration of impaired leaky vessels.
conclusionThe vascular fragility of Fli-1 ECKO mice was improved by bosentan through the normalization of Fli-1 protein levels and activity in endothelial cells, which may explain, in part, the mechanism underlying the beneficial effects of endothelin receptor blockade on SSc vasculopathy.
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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.