ArticleRheumatology (Oxford, England)2020
Extracellular SPARC cooperates with TGF-β signalling to induce pro-fibrotic activation of systemic sclerosis patient dermal fibroblasts.
Article in Rheumatology (Oxford, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Key regulatory elements of the TGFβ-LRRC15 axis predict disease progression and immunotherapy resistance across cancer types.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Transforming growth factor-β1 promotes initiation of entheseal pathological bone formation via osteonectin induction in ankylosing spondylitis.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Article
- Exploring the common ferroptosis-related genes and molecular mechanisms in periodontitis and systemic sclerosis via integrated bioinformatics and experimental analysis.Frontiers in cell and developmental biology · 2026Article
- Field Marigold (Calendula arvensis L.) accelerates wound-healing in vivo: role of transforming growth factor-beta1 (TGF-β1), inflammatory, and biochemical molecules.Journal of molecular histology · 2025Article
- Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis.Scientific reports · 2025Article
- Pan-cancer secreted proteome and skeletal muscle regulation: insight from a proteogenomic data-driven knowledge base.Functional & integrative genomics · 2025Review
- Elevated Serum Extracellular Vesicle-Packaged SPARC in Hypertension: A Cross-Sectional Study in a Middle-Aged and Elderly Population.Journal of clinical hypertension (Greenwich, Conn.) · 2025Article
- SPARC activates p38γ signaling to promote PFKFB3 protein stabilization and contributes to keloid fibroblast glycolysis.Inflammation and regeneration · 2024Article
- Unraveling the Pathogenesis of Calcinosis in Systemic Sclerosis: A Molecular and Clinical Insight.International journal of molecular sciences · 2024Review
- Relationships between Osteopontin, Osteoprotegerin, and Other Extracellular Matrix Proteins in Calcifying Arteries.Biomedicines · 2024Article
- Suppression of SPARC Ameliorates Ovalbumin-induced Airway Remodeling via TGFβ1/Smad2 in Chronic Asthma.Allergy, asthma & immunology research · 2024Article
- The role of SPARC (secreted protein acidic and rich in cysteine) in the pathogenesis of obesity, type 2 diabetes, and non-alcoholic fatty liver disease.Journal of physiology and biochemistry · 2023Review
- SPARC Is Highly Expressed in Young Skin and Promotes Extracellular Matrix Integrity in Fibroblasts via the TGF-β Signaling Pathway.International journal of molecular sciences · 2023Article
- Characterization of bioactive substances involved in the induction of bone augmentation using demineralized bone sheets.International journal of implant dentistry · 2022Article
- Human Metabolites ofFrontiers in pharmacology · 2021Article
- Emerging Roles of Matricellular Proteins in Systemic Sclerosis.International journal of molecular sciences · 2020Review
- Pathogenic Roles of Autoantibodies and Aberrant Epigenetic Regulation of Immune and Connective Tissue Cells in the Tissue Fibrosis of Patients with Systemic Sclerosis.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesSSc is an autoimmune disease characterized by inflammation, vascular injury and excessive fibrosis in multiple organs. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein that regulates processes involved in SSc pathology, such as inflammation and fibrosis. In vivo and in vitro studies have implicated SPARC in SSc, but it is unclear if the pro-fibrotic effects of SPARC on fibroblasts are a result of intracellular signalling or fibroblast interactions with extracellular SPARC hampering further development of SPARC as a potential therapeutic target. This study aimed to analyse the potential role of exogenous SPARC as a regulator of fibrosis in SSc.
methodsDermal fibroblasts from both healthy controls and SSc patients were stimulated with SPARC alone or in combination with TGF-β1, in the absence or presence of a TGF receptor 1 inhibitor. mRNA and protein expression of extracellular matrix components and other fibrosis-related mediators were measured by quantitative PCR and western blot.
resultsExogenous SPARC induced mRNA and protein expression of collagen I, collagen IV, fibronectin 1, TGF-β and SPARC by dermal fibroblasts from SSc patients, but not from healthy controls. Importantly, exogenous SPARC induced the activation of the tyrosine kinase SMAD2 and pro-fibrotic gene expression induced by SPARC in SSc fibroblasts was abrogated by inhibition of TGF-β signalling.
conclusionThese results indicate that exogenous SPARC is an important pro-fibrotic mediator contributing to the pathology driving SSc but in a TGF-β dependent manner. Therefore, SPARC could be a promising therapeutic target for reducing fibrosis in SSc patients, even in late states of the disease.
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