ArticleCirculation2008
Transcriptional regulation of Bim by FOXO3a and Akt mediates scleroderma serum-induced apoptosis in endothelial progenitor cells.
Article in Circulation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 88 citations in OpenAlex.
- Systemic Sclerosis: A Key Model of Endothelial Dysfunction.Biomedicines · 2025Review
- Pathogenesis of systemic sclerosis: an integrative review of recent advances.Journal of rheumatic diseases · 2025Review
- Endothelial Progenitor Cells in Autoimmune Disorders.Stem cell reviews and reports · 2023Review
- Endothelial Dysfunction in Systemic Sclerosis.International journal of molecular sciences · 2023Review
- A VEGFB-Based Peptidomimetic Inhibits VEGFR2-Mediated PI3K/Akt/mTOR and PLCγ/ERK Signaling and Elicits Apoptotic, Antiangiogenic, and Antitumor Activities.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Article
- Kcnh2 mediates FAK/AKT-FOXO3A pathway to attenuate sepsis-induced cardiac dysfunction.Cell proliferation · 2021Article
- Endothelial cells and endothelial progenitor cells in the pathogenesis of systemic sclerosis.European journal of rheumatology · 2020Review
- CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma.Cancer biology & medicine · 2020Article
- An Autoimmune Basis for Raynaud's Phenomenon: Murine Model and Human Disease.Arthritis & rheumatology (Hoboken, N.J.) · 2018Article
- JNK1 as a signaling node in VDR-BRAF induction of cell death in AML.The Journal of steroid biochemistry and molecular biology · 2018Article
- The Activation of Human Dermal Microvascular Cells by Poly(I:C), Lipopolysaccharide, Imiquimod, and ODN2395 Is Mediated by the Fli1/FOXO3A Pathway.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- The Role of Endothelial Progenitors in the Repair of Vascular Damage in Systemic Sclerosis.Frontiers in immunology · 2018Review
- Increased serum levels of fractalkine and mobilisation of CD34Arthritis research & therapy · 2017Observational
- Suppression of Excessive Histone Deacetylases Activity in Diabetic Hearts Attenuates Myocardial Ischemia/Reperfusion Injury via Mitochondria Apoptosis Pathway.Journal of diabetes research · 2017Article
- Scleroderma dermal microvascular endothelial cells exhibit defective response to pro-angiogenic chemokines.Rheumatology (Oxford, England) · 2016Article
- BAFF promotes proliferation of human mesangial cells through interaction with BAFF-R.BMC nephrology · 2015Article
- Cellular interactions in the pathogenesis of interstitial lung diseases.European respiratory review : an official journal of the European Respiratory Society · 2015Review
- Pathogenesis of Systemic Sclerosis.Frontiers in immunology · 2015Review
- CD28-mediated pro-survival signaling induces chemotherapeutic resistance in multiple myeloma.Blood · 2014Article
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7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEndothelial progenitor cells (EPCs) contribute to vascular regeneration/repair and thus may protect against scleroderma vasculopathy. We aimed to determine whether circulating EPCs were reduced in scleroderma, whether scleroderma sera could induce EPC apoptosis, and, if so, what the underlying apoptotic signaling pathway was. METHODS AND
resultsCirculating EPC levels were quantified in 54 patients with scleroderma and 18 healthy control subjects by colony-forming unit assay and flow cytometry, which revealed markedly decreased EPC levels in scleroderma patients relative to healthy subjects. Substantial apoptosis was detected in EPCs after culturing in the presence of scleroderma sera compared with normal sera. Intriguingly, depletion of the IgG fraction from scleroderma sera completely abolished the apoptotic effects. Furthermore, scleroderma sera inhibited the activation/phosphorylation of Akt, which in turn suppressed the phosphorylation and degradation of forkhead transcription factor FKHRL1 (FOXO3a), resulting in the upregulation of apoptotic protein Bim. siRNA-mediated FOXO3a and Bim knockdown substantially reduced scleroderma serum-induced EPC apoptosis. Importantly, Bim expression and baseline apoptosis were increased in EPCs freshly isolated from scleroderma patients relative to that obtained from healthy subjects.
conclusionsScleroderma serum-induced EPC apoptosis is mediated chiefly by the Akt-FOXO3a-Bim pathway, which may account, at least in part, for the decreased circulating EPC levels in scleroderma patients.
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