ArticleArthritis research & therapy2018
Effects of selexipag and its active metabolite in contrasting the profibrotic myofibroblast activity in cultured scleroderma skin fibroblasts.
Article in Arthritis research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Efficacy of different pharmacological therapies for diffuse cutaneous systemic sclerosis: a systematic review and network meta-analysis.European journal of clinical pharmacology · 2026Pooled it
- A selective agonist of the prostacyclin receptor alleviates microglial and astroglial neuroinflammatory responses through P38 and NLRP3.Frontiers in immunology · 2026Article
- [Tofacitinib inhibits the transformation of lung fibroblasts into myofibroblasts through JAK/STAT3 pathway].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2024Article
- Biomarkers in Systemic Sclerosis: An Overview.Current issues in molecular biology · 2023Review
- The Role of SOX9 in IGF-II-Mediated Pulmonary Fibrosis.International journal of molecular sciences · 2023Article
- Zoledronic Acid Targeting of the Mevalonate Pathway Causes Reduced Cell Recruitment and Attenuates Pulmonary Fibrosis.Frontiers in pharmacology · 2022Article
- Umbilical Cord Mesenchymal Stem Cells for Inhibiting the Fibrosis and Autoimmune Development in HOCl-Induced Systemic Scleroderma Mouse Model.International journal of stem cells · 2021Article
- Nintedanib downregulates the transition of cultured systemic sclerosis fibrocytes into myofibroblasts and their pro-fibrotic activity.Arthritis research & therapy · 2021Article
- The Updated Role of Ultrasound in Assessing Dermatological Manifestations in Systemic Sclerosis.Open access rheumatology : research and reviews · 2021Review
- Correlation between circulating fibrocytes and dermal thickness in limited cutaneous systemic sclerosis patients: a pilot study.Rheumatology international · 2019Article
- Cathepsin S regulates renal fibrosis in mouse models of mild and severe hydronephrosis.Molecular medicine reports · 2019Article
- Emerging targets of disease-modifying therapy for systemic sclerosis.Nature reviews. Rheumatology · 2019Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMyofibroblasts contribute to fibrosis through the overproduction of extracellular matrix (ECM) proteins, primarily type I collagen (COL-1) and fibronectin (FN), a process which is mediated in systemic sclerosis (SSc) by the activation of fibrogenic intracellular signaling transduction molecules, including extracellular signal-regulated kinases 1 and 2 (Erk1/2) and protein kinase B (Akt). Selexipag is a prostacyclin receptor agonist synthesized for the treatment of pulmonary arterial hypertension. The study investigated the possibility for selexipag and its active metabolite (ACT-333679) to downregulate the profibrotic activity in primary cultures of SSc fibroblasts/myofibroblasts and the fibrogenic signaling molecules involved.
methodsFibroblasts from skin biopsies obtained with Ethics Committee (EC) approval from patients with SSc, after giving signed informed consent, were cultured until the 3
resultsSelexipag and ACT-333679 significantly reduced protein synthesis and gene expression of α-SMA, S100A4, and COL-1 in cultured SSc fibroblasts/myofibroblasts compared to untreated cells, whereas FN was significantly downregulated at the protein level. Interestingly, ACT-333679 significantly reduced the phosphorylation of Erk1/2 and Akt in cultured SSc fibroblasts/myofibroblasts.
conclusionsSelexipag and mainly its active metabolite ACT-333679 were found for the first time to potentially interfere with the profibrotic activity of cultured SSc fibroblasts/myofibroblasts at least in vitro, possibly through the downregulation of fibrogenic Erk1/2 and Akt signaling molecules.
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