ArticleJournal of dermatological science2012
Acid sphingomyelinase deficiency contributes to resistance of scleroderma fibroblasts to Fas-mediated apoptosis.
Article in Journal of dermatological science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Pathological Interplay of ROS With Myofibroblasts: An Impediment to Corneal Restitution.Oxidative medicine and cellular longevity · 2026Review
- Mesenchymal stem cells alleviate pulmonary fibrosis and gut microbiota dysbiosis in systemic sclerosis.Frontiers in microbiology · 2025Article
- The Role of Autophagy and Apoptosis in Affected Skin and Lungs in Patients with Systemic Sclerosis.International journal of molecular sciences · 2023Review
- Ceramides in Autoimmune Rheumatic Diseases: Existing Evidence and Therapeutic Considerations for Diet as an Anticeramide Treatment.Nutrients · 2023Review
- Pathophysiology of systemic sclerosis (scleroderma).The Kaohsiung journal of medical sciences · 2022Review
- Myofibroblast fate plasticity in tissue repair and fibrosis: Deactivation, apoptosis, senescence and reprogramming.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2021Article
- Natural Formulations: Novel Viewpoint for Scleroderma Adjunct Treatment.Journal of immunology research · 2021Review
- Evasion of apoptosis by myofibroblasts: a hallmark of fibrotic diseases.Nature reviews. Rheumatology · 2020Review
- Regulation of fibroblast Fas expression by soluble and mechanical pro-fibrotic stimuli.Respiratory research · 2018Article
- Unraveling SSc Pathophysiology; The Myofibroblast.Frontiers in immunology · 2018Review
- Article
- Burn injury influences the T cell homeostasis in a butyrate-acid sphingomyelinase dependent manner.Cellular immunology · 2017Article
- Updates on morphea: role of vascular injury and advances in treatment.Autoimmune diseases · 2013Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundScleroderma (SSc) is characterized by excess production and deposition of extracellular matrix (ECM) proteins. Activated fibroblasts play a key role in fibrosis in SSc and are resistant to Fas-mediated apoptosis. Acid sphingomyelinase (ASMase), a major sphingolipid enzyme, plays an important role in the Fas-mediated apoptosis.
objectiveWe investigated whether dysregulation of ASMase contributes to Fas-mediated apoptosis resistance in SSc fibroblasts.
methodsFibroblasts were isolated from SSc patients and healthy controls. Western blot was performed to analyze protein levels and quantitative real time RT-PCR was used to determine mRNA expression. Cells were transiently transfected with siRNA oligos against ASMase or transduced with adenoviruses overexpressing ASMase. Apoptosis was induced using anti-Fas antibody (1 μg/mL) and analyzed using caspase-3 antibody or Cell Death Detection ELISA.
resultsSSc fibroblasts showed increased resistance to Fas-mediated apoptosis. ASMase expression was decreased in SSc fibroblasts and Transforming Growth Factor beta (TGFβ), the major fibrogenic cytokine involved in the pathogenesis of SSc, downregulated ASMase in normal fibroblasts. Forced expression of ASMase in SSc fibroblasts restored sensitivity of these cells to Fas-mediated apoptosis while blockade of ASMase was sufficient to induce partial resistance to Fas-induced apoptosis in normal fibroblasts. In addition, ASMase blockade decreased activity of protein phosphatase 2A (PP2A) through phosphorylation on Tyr(307) and resulted in activation of extracellular regulated kinase 1/2 (Erk1/2) and protein kinase B (Akt/PKB).
conclusionIn conclusion, this study suggests that ASMase deficiency promotes apoptosis resistance and contributes to activation of profibrotic signaling in SSc fibroblasts.
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