ArticleArthritis & rheumatology (Hoboken, N.J.)2015
Increased expression of NAPDH oxidase 4 in systemic sclerosis dermal fibroblasts: regulation by transforming growth factor β.
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 29 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- Lipoaspirate-derived secretome restores redox homeostasis to attenuate pathological scar formation.Stem cell research & therapy · 2026Article
- Laser-induced skin microenvironment remodeling via exosomal CEBPA-mediated crosstalk between keratinocyte and fibroblast.Journal of nanobiotechnology · 2026Article
- The effect of salubrinal on the endoplasmic reticulum stress pathway in heat-stressed spermatogonial cells in vitro.FEBS open bio · 2026Article
- A review of recent studies on the pathogenesis of Systemic Sclerosis: focus on fibrosis pathways.Frontiers in immunology · 2025Review
- [Expression and significance of ferroptosis marker 4-HNE inBeijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2024Article
- Phosphodiesterase 4 is overexpressed in keloid epidermal scars and its inhibition reduces keratinocyte fibrotic alterations.Molecular medicine (Cambridge, Mass.) · 2024Article
- miR-146a Decreases Inflammation and ROS Production in Aged Dermal Fibroblasts.International journal of molecular sciences · 2024Article
- [An artificial neural network diagnostic model for scleroderma and immune cell infiltration analysis based on mitochondria-associated genes].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Development and validation of a new diagnostic prediction model of ENHO and NOX4 for early diagnosis of systemic sclerosis.Frontiers in immunology · 2024Article
- Higher gamma-glutamyl transferase levels are associated with an increased risk of incident systemic sclerosis: a nationwide population-based study.Scientific reports · 2023Article
- Oxidative Stress and Epigenetics: miRNA Involvement in Rare Autoimmune Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Oxidative stress promotes fibrosis in systemic sclerosis through stabilization of a kinase-phosphatase complex.JCI insight · 2022Article
- Pyrrosia petiolosa Extract Ameliorates Ethylene Glycol-Induced Urolithiasis in Rats by Inhibiting Oxidative Stress and Inflammatory Response.Disease markers · 2022Article
- Review
- IL11 is elevated in systemic sclerosis and IL11-dependent ERK signalling underlies TGFβ-mediated activation of dermal fibroblasts.Rheumatology (Oxford, England) · 2021Article
- Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target.Journal of clinical medicine · 2021Review
- Reactive Oxygen Species and Oxidative Stress in the Pathogenesis and Progression of Genetic Diseases of the Connective Tissue.Antioxidants (Basel, Switzerland) · 2020Review
- Brd4-p300 inhibition downregulates Nox4 and accelerates lung fibrosis resolution in aged mice.JCI insight · 2020Article
- Activin A-Mediated Regulation of XT-I in Human Skin Fibroblasts.Biomolecules · 2020Article
- Microparticles in systemic sclerosis, targets or tools to control fibrosis: This is the question!Journal of scleroderma and related disorders · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveSystemic sclerosis (SSc) is characterized by severe and often progressive fibrosis of the skin and multiple internal organs. The mechanisms responsible for these alterations remain obscure, although excessive reactive oxygen species (ROS)-mediated oxidative stress has been implicated. NOX-4 is 1 of 7 isoforms of NADPH oxidase responsible for the generation of ROS. The purpose of this study was to examine NOX-4 expression in skin and cultured dermal fibroblasts from SSc patients and to examine its regulation by transforming growth factor β1 (TGFβ1).
methodsNOX-4 was assessed in normal and SSc skin by immunohistologic analysis and in normal and SSc cultured dermal fibroblasts by quantitative polymerase chain reaction analysis, fluorescence microscopy, and Western blotting. ROS levels were assessed by fluorescence measurement of H2 O2 production. Specific kinase inhibitors were used to study the TGFβ1 signaling involved in NOX-4 stimulation. NOX-4 inhibition/down-regulation was induced with a selective NOX-4 small-molecule inhibitor and NOX-4 small interfering RNA (siRNA).
resultsIn contrast with normal skin fibroblasts, those from SSc skin showed intense NOX-4 staining. Cultured SSc fibroblasts displayed increased NOX-4 expression. TGFβ1 caused potent NOX-4 protein and messenger RNA stimulation in normal and SSc fibroblasts, which was mediated by the protein kinase Cδ (PKCδ) and Smad2/3 pathways. NOX-4 knockdown in SSc fibroblasts reduced the production of ROS and lowered the expression of type I collagen.
conclusionNOX-4 expression and production were found to be constitutively elevated in SSc skin and cultured SSc dermal fibroblasts. TGFβ1 stimulated NOX-4 expression in normal and SSc fibroblasts through PKCδ and Smad2/3 signaling pathways. A small-molecule NOX-4 inhibitor decreased collagen and fibronectin production by normal and SSc fibroblasts, and NOX-4 siRNA knockdown reduced ROS and collagen production by SSc fibroblasts. These results demonstrate the involvement of NOX-4 in SSc-associated fibrosis and indicate NOX-4 inhibitors as novel therapeutic approaches for SSc.
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