ArticleArthritis & rheumatology (Hoboken, N.J.)2015
Fibrosis, vascular activation, and immune abnormalities resembling systemic sclerosis in bleomycin-treated Fli-1-haploinsufficient mice.
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 39 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
39 citing papers in PubMed, 86 citations in OpenAlex.
- Role of Transcription Factor Fli-1 in Inflammation and Autoimmune Diseases.Biomolecules · 2025Review
- Comparative Evaluation of Bleomycin- and Collagen-V-Induced Models of Systemic Sclerosis: Insights into Fibrosis and Autoimmunity for Translational Research.International journal of molecular sciences · 2025Article
- Recent Insights into Cellular and Molecular Mechanisms of Defective Angiogenesis in Systemic Sclerosis.Biomedicines · 2024Review
- Transcription Factors in the Pathogenesis of Lupus Nephritis and Their Targeted Therapy.International journal of molecular sciences · 2024Review
- The modulation of immune cell death in connection to microRNAs and natural products.Frontiers in immunology · 2024Review
- The Role of Immune Cells in the Pathogenesis of Idiopathic Pulmonary Fibrosis.Medicina (Kaunas, Lithuania) · 2023Review
- M2 macrophage polarization in systemic sclerosis fibrosis: pathogenic mechanisms and therapeutic effects.Heliyon · 2023Review
- 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
- ADAR1 promotes systemic sclerosisFrontiers in immunology · 2022Article
- Endothelial CCR6 expression due to FLI1 deficiency contributes to vasculopathy associated with systemic sclerosis.Arthritis research & therapy · 2021Article
- Umbilical Cord Mesenchymal Stem Cells for Inhibiting the Fibrosis and Autoimmune Development in HOCl-Induced Systemic Scleroderma Mouse Model.International journal of stem cells · 2021Article
- Endothelial-to-mesenchymal transition in systemic sclerosis.Clinical and experimental immunology · 2021Review
- New Insights into Profibrotic Myofibroblast Formation in Systemic Sclerosis: When the Vascular Wall Becomes the Enemy.Life (Basel, Switzerland) · 2021Review
- 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
- The contribution of mesenchymal transitions to the pathogenesis of systemic sclerosis.European journal of rheumatology · 2020Review
- The Pathogenesis of Systemic Sclerosis: An Understanding Based on a Common Pathologic Cascade across Multiple Organs and Additional Organ-Specific Pathologies.Journal of clinical medicine · 2020Review
- Semaphorin 7A promotes endothelial to mesenchymal transition through ATF3 mediated TGF-β2/Smad signaling.Cell death & disease · 2020Article
- A Flowable Placental Formulation Prevents Bleomycin-Induced Dermal Fibrosis in Aged Mice.International journal of molecular sciences · 2020Article
- Evolving insights into the cellular and molecular pathogenesis of fibrosis in systemic sclerosis.Translational research : the journal of laboratory and clinical medicine · 2019Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveFli-1, a potential predisposing factor for systemic sclerosis (SSc), is constitutively down-regulated in the lesional skin of patients with SSc by an epigenetic mechanism. To investigate the impact of Fli-1 deficiency on the induction of an SSc phenotype in various cell types, we generated bleomycin-induced skin fibrosis in Fli-1(+/-) mice and investigated the molecular mechanisms underlying its phenotypic alterations.
methodsMessenger RNA (mRNA) levels and protein expression of target molecules were examined by quantitative reverse transcription-polymerase chain reaction and immunostaining. Transforming growth factor β (TGFβ) bioassay was used to evaluate the activation of latent TGFβ. The binding of Fli-1 to the target gene promoters was assessed with chromatin immunoprecipitation.
resultsBleomycin induced more severe dermal fibrosis in Fli-1(+/-) mice than in wild-type mice. Fli-1 haploinsufficiency activated dermal fibroblasts via the up-regulation of αvβ3 and αvβ5 integrins and activation of latent TGFβ. Dermal fibrosis in Fli-1(+/-) mice was also attributable to endothelial-to-mesenchymal transition, which is directly induced by Fli-1 deficiency and amplified by bleomycin. Th2/Th17-skewed inflammation and increased infiltration of mast cells and macrophages were seen, partly due to the altered expression of cell adhesion molecules in endothelial cells as well as the induction of the skin chemokines. Fli-1(+/-) mouse macrophages preferentially differentiated into an M2 phenotype upon stimulation with interleukin-4 (IL-4) or IL-13.
conclusionOur findings provide strong evidence for the fundamental role of Fli-1 deficiency in inducing SSc-like phenotypic alterations in dermal fibroblasts, endothelial cells, and macrophages in a manner consistent with human disease.
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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.