ArticleArthritis and rheumatism2012
Effect of oxidative stress on protein tyrosine phosphatase 1B in scleroderma dermal fibroblasts.
Article in Arthritis and rheumatism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 44 citations in OpenAlex.
- Drugging the redox-regulated immunoproteome.Nature chemical biology · 2026Article
- Plant-Derived Agents and Systemic Sclerosis: A Systematic Review of Therapeutic Potential and Molecular Mechanisms.Current issues in molecular biology · 2026Review
- PTP1B Modulates Carotid Plaque Vulnerability in Atherosclerosis Through Rab5-PDGFRβ-Mediated Endocytosis Disruption and Apoptosis.CNS neuroscience & therapeutics · 2024Article
- Redox Pathogenesis in Rheumatic Diseases.ACR open rheumatology · 2024Review
- 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
- Microvasculopathy-Related Hemorrhagic Tissue Deposition of Iron May Contribute to Fibrosis in Systemic Sclerosis: Hypothesis-Generating Insights from the Literature and Preliminary Findings.Life (Basel, Switzerland) · 2022Article
- 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
- Iloprost Attenuates Oxidative Stress-Dependent Activation of Collagen Synthesis Induced by Sera from Scleroderma Patients in Human Pulmonary Microvascular Endothelial Cells.Molecules (Basel, Switzerland) · 2021Article
- Review
- Natural Formulations: Novel Viewpoint for Scleroderma Adjunct Treatment.Journal of immunology research · 2021Review
- DNA Damage Response and Oxidative Stress in Systemic Autoimmunity.International journal of molecular sciences · 2019Review
- Oxidative stress in the pathogenesis of systemic scleroderma: An overview.Journal of cellular and molecular medicine · 2018Review
- PTP4A1 promotes TGFβ signaling and fibrosis in systemic sclerosis.Nature communications · 2017Article
- Protein Tyrosine Phosphatases in Systemic Sclerosis: Potential Pathogenic Players and Therapeutic Targets.Current rheumatology reports · 2017Review
- 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
- Genome-wide DNA methylation analysis in dermal fibroblasts from patients with diffuse and limited systemic sclerosis reveals common and subset-specific DNA methylation aberrancies.Annals of the rheumatic diseases · 2015Article
- Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.Current rheumatology reports · 2015Review
- Serum prolidase enzyme activity and oxidative status in patients with fibromyalgia.Redox report : communications in free radical research · 2014Article
- Oxidative stress-associated protein tyrosine kinases and phosphatases in Fanconi anemia.Antioxidants & redox signaling · 2014Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
objectivePlatelet-derived growth factor (PDGF) and its receptor, PDGFR, promote fibrosis in systemic sclerosis (SSc; scleroderma) dermal fibroblasts, and such cells in scleroderma skin lesions produce excessive reactive oxygen species (ROS). PDGFR is phosphorylated upon PDGF stimulation, and is dephosphorylated by protein tyrosine phosphatases (PTPs), including PTP1B. This study was undertaken to determine whether the thiol-sensitive PTP1B is affected by ROS in SSc dermal fibroblasts, thereby enhancing the phosphorylation of PDGFR and synthesis of type I collagen. This study also sought to investigate the effect of a thiol antioxidant, N-acetylcysteine (NAC), in SSc.
methodsFibroblasts were isolated from the skin of patients with diffuse SSc and normal healthy donors for cell culture experiments and immunofluorescence analyses. A phosphate release assay was used to determine the activity of PTP1B.
resultsLevels of ROS and type I collagen were significantly higher and amounts of free thiol were significantly lower in SSc fibroblasts compared to normal fibroblasts. After stimulation with PDGF, not only were PDGFR and ERK-1/2 phosphorylated to a greater extent, but also the ability to produce PTP1B was hampered in SSc fibroblasts. The activity of PTP1B was significantly inactivated in SSc fibroblasts as a result of cysteine oxidation by the raised levels of ROS, which was confirmed by the oxidation of multiple PTPs, including PTP1B, in SSc fibroblasts. Decreased expression of PTP1B in normal fibroblasts led to increased expression of type I collagen. Treatment of the cells with NAC restored the activity of PTP1B, improved the profile of PDGFR phosphorylation, decreased the numbers of tyrosine-phosphorylated proteins and levels of type I collagen, and scavenged ROS in SSc fibroblasts.
conclusionThis study describes a new mechanism by which ROS may promote a profibrotic phenotype in SSc fibroblasts through the oxidative inactivation of PTP1B, leading to pronounced activation of PDGFR. The study also presents a novel molecular mechanism by which NAC may act on ROS and PTP1B to provide therapeutic benefit in SSc.
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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.