ArticleRheumatology (Oxford, England)2017
Scleroderma keratinocytes promote fibroblast activation independent of transforming growth factor beta.
Article in Rheumatology (Oxford, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Interplay Between Keratinocytes and Fibroblasts: A Systematic Review Providing a New Angle for Understanding Skin Fibrotic Disorders.Frontiers in immunology · 2020Pooled it
- Tofacitinib blocks IFN-regulated biomarker genes in skin fibroblasts and keratinocytes in a systemic sclerosis trial.JCI insight · 2022Trial
- Keratinocytes: A key player in skin immunity and their emerging roles in secondary lymphedema.JID innovations : skin science from molecules to population health · 2026Review
- Keratinocytes: pleiotropic orchestrators of cutaneous immunity and Inflammation - Emerging therapeutic paradigms in dermatological pathologies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Transforming growth factor beta (TGF-β) induces type 1 interferon signalling in systemic sclerosis keratinocytes through the chloride intracellular channel 4 (CLIC4).Arthritis research & therapy · 2025Article
- A Paradigm Shift in SSTI Management: The Multifunctional Role of Extracellular Vesicles.International journal of molecular sciences · 2025Review
- Fibrosis: cross-organ biology and pathways to development of innovative drugs.Nature reviews. Drug discovery · 2025Review
- Review
- Aberrant Chitinase 3-Like 1 Expression in Basal Cells Contributes to Systemic Sclerosis Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Regulation of involucrin and signalling pathway in scleroderma epidermal keratinocytes.Postepy dermatologii i alergologii · 2024Article
- Critical Analysis of Cytoplasmic Progression of Inflammatory Signaling Suggests Potential Pharmacologic Targets for Wound Healing and Fibrotic Disorders.Biomedicines · 2024Review
- The Central Roles of Keratinocytes in Coordinating Skin Immunity.The Journal of investigative dermatology · 2024Review
- Clinical, Histologic, and Transcriptomic Evaluation of Sequential Fat Grafting for Morphea: A Nonrandomized Controlled Trial.JAMA dermatology · 2024Article
- Current Concepts on the Pathogenesis of Systemic Sclerosis.Clinical reviews in allergy & immunology · 2023Review
- Extracellular matrix stiffness-The central cue for skin fibrosis.Frontiers in molecular biosciences · 2023Review
- Induction of pro-inflammatory genes by fibronectin DAMPs in three fibroblast cell lines: Role of TAK1 and MAP kinases.PloS one · 2023Article
- Centromere defects, chromosome instability, and cGAS-STING activation in systemic sclerosis.Nature communications · 2022Article
- Contribution of keratinocytes to dermal fibrosis.Current opinion in rheumatology · 2022Review
- Autologous hematopoietic stem cell transplantation promotes connective tissue remodeling in systemic sclerosis patients.Arthritis research & therapy · 2022Article
- Altered Cellular Immunity and Differentially Expressed Immune-Related Genes in Patients With Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Objectives: SSc is a devastating disease that results in fibrosis of the skin and other organs. Fibroblasts are a key driver of the fibrotic process through deposition of extracellular matrix. The mechanisms by which fibroblasts are induced to become pro-fibrotic remain unclear. Thus, we examined the ability of SSc keratinocytes to promote fibroblast activation and the source of this effect. Methods: Keratinocytes were isolated from skin biopsies of 9 lcSSc, 10 dcSSc and 13 control patients. Conditioned media was saved from the cultures. Normal fresh primary fibroblasts were exposed to healthy control and SSc keratinocyte conditioned media in the presence or absence of neutralizing antibodies for TGF-β. Gene expression was assessed by microarrays and real-time PCR. Immunocytochemistry was performed for α-smooth muscle actin (α-SMA), collagen type 1 (COL1A1) and CCL5 expression. Results: SSc keratinocyte conditioned media promoted fibroblast activation, characterized by increased α-SMA and COL1A1 mRNA and protein expression. This effect was independent of TGF-β. Microarray analysis identified upregulation of nuclear factor κB (NF-κB) and downregulation of peroxisome proliferator-activated receptor γ (PPAR-γ) pathways in both SSc subtypes. Scleroderma keratinocytes exhibited increased expression of NF-κB-regulated cytokines and chemokines and lesional skin staining confirmed upregulation of CCL5 in basal keratinocytes. Conclusion: Scleroderma keratinocytes promote the activation of fibroblasts in a TGF-β-independent manner and demonstrate an imbalance in NF-κB1 and PPAR-γ expression leading to increased cytokine and CCL5 production. Further study of keratinocyte mediators of fibrosis, including CCL5, may provide novel targets for skin fibrosis therapy.
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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.