ArticleJournal of cellular physiology2013
Interferon-γ promotes vascular remodeling in human microvascular endothelial cells by upregulating endothelin (ET)-1 and transforming growth factor (TGF) β2.
Article in Journal of cellular physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 90 citations in OpenAlex.
- IFN-γ drives inflammatory bowel disease pathogenesis through VE-cadherin-directed vascular barrier disruption.The Journal of clinical investigation · 2019Trial
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- MK2 Inhibition in CD4+ T Cells Protects Against IFNγ and IL-17A, Chronic Inflammation, and Fibrosis in Inflammatory Bowel Disease Models.Inflammatory bowel diseases · 2025Article
- Therapeutic effect of bosentan on 2, 4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model.Archives of dermatological research · 2025Article
- Cxcl9 modulates aging associated microvascular metabolic and angiogenic dysfunctions in subcutaneous adipose tissue.Angiogenesis · 2025Article
- Cellular Transdifferentiation: A Crucial Mechanism of Fibrosis in Systemic Sclerosis.Current rheumatology reviews · 2024Review
- Endothelial cells are a key target of IFN-g during response to combined PD-1/CTLA-4 ICB treatment in a mouse model of bladder cancer.iScience · 2023Article
- The Pathogenesis of Systemic Sclerosis: The Origin of Fibrosis and Interlink with Vasculopathy and Autoimmunity.International journal of molecular sciences · 2023Review
- Endothelial to mesenchymal transition in neonatal hyperoxic lung injury: role of sex as a biological variable.Physiological genomics · 2023Article
- Epithelial-Mesenchymal Plasticity and Endothelial-Mesenchymal Transition in Cutaneous Wound Healing.Cold Spring Harbor perspectives in biology · 2023Review
- New insights into maladaptive vascular responses to donor specific HLA antibodies in organ transplantation.Frontiers in transplantation · 2023Review
- An emerging view on vascular fibrosis molecular mediators and relevant disorders: from bench to bed.Frontiers in cardiovascular medicine · 2023Review
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- The lncRNA PRINS-miRNA-mRNA Axis Gene Expression Profile as a Circulating Biomarker Panel in Psoriasis.Molecular diagnosis & therapy · 2022Article
- Sphingosine 1-phosphate receptor-targeted therapeutics in rheumatic diseases.Nature reviews. Rheumatology · 2022Review
- Transient Opening of the Blood-Brain Barrier by Vasoactive Peptides to Increase CNS Drug Delivery: Reality Versus Wishful Thinking?Current neuropharmacology · 2022Review
- Modeling alpha-synuclein pathology in a human brain-chip to assess blood-brain barrier disruption.Nature communications · 2021Article
- Endothelial-to-mesenchymal transition in systemic sclerosis.Clinical and experimental immunology · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Systemic sclerosis (SSc) is a complex disease characterized by vascular alterations, activation of the immune system and tissue fibrosis. Previous studies have implicated activation of the interferon pathways in the pathogenesis of SSc. The goal of this study was to determine whether interferon type I and/or type II could play a pathogenic role in SSc vasculopathy. Human dermal microvascular endothelial cells (HDMVECs) and fibroblasts were obtained from foreskins of healthy newborns. The RT Profiler PCR Array System was utilized to screen for EndoMT genes. Treatment with IFN-α or IFN-γ downregulated Fli1 and VE-cadherin. In contrast, IFN-α and IFN-γ exerted opposite effects on the expression of α-SMA, CTGF, ET-1, and TGFβ2, with IFN-α downregulating and IFN-γ upregulating this set of genes. Blockade of TGFβ signaling normalized IFN-γ-mediated changes in Fli1, VE-cadherin, CTGF, and ET-1 levels, whereas upregulation of α-SMA and TGFβ2 was not affected. Bosentan treatment was more effective than TGFβ blockade in reversing the actions of IFN-γ, including downregulation of α-SMA and TGFβ2, suggesting that activation of the ET-1 pathway plays a main role in the IFN-γ responses in HDMECs. IFN-γ induced expression of selected genes related to endothelial-to-mesenchymal transition (EndoMT), including Snail1, FN1, PAI1, TWIST1, STAT3, RGS2, and components of the WNT pathway. The effect of IFN-γ on EndoMT was mediated via TGFβ2 and ET-1 signaling pathways. This study demonstrates distinct effects of IFN-α and IFN-γ on the biology of vascular endothelial cells. IFN-γ may contribute to abnormal vascular remodeling and fibrogenesis in SSc, partially via induction of EndoMT.
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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.