ArticleCell death & disease2016
TWEAK favors phosphate-induced calcification of vascular smooth muscle cells through canonical and non-canonical activation of NFκB.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- In Vitro Analysis of TWEAK/Fn14 Axis in the Blood-Brain Barrier Models during Oxygen-Glucose Deprivation and Reoxygenation.Molecular neurobiology · 2026Article
- TWEAK/Fn14 axis may promote vascular smooth muscle cell senescence via p38 signaling pathway: preliminary evidence.Future science OA · 2025Article
- Associations between systemic inflammation response index and abdominal aortic calcification: a cross-sectional study.Scientific reports · 2025Article
- The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia.Cancer cell · 2024Article
- Paricalcitol Has a Potent Anti-Inflammatory Effect in Rat Endothelial Denudation-Induced Intimal Hyperplasia.International journal of molecular sciences · 2024Article
- Extracellular Vesicle-Associated TWEAK Contributes to Vascular Inflammation and Remodeling During Acute Cellular Rejection.JACC. Basic to translational science · 2023Article
- Article
- The TWEAK/Fn14/CD163 axis-implications for metabolic disease.Reviews in endocrine & metabolic disorders · 2022Review
- Phosphate Burden and Inflammation.Advances in experimental medicine and biology · 2022Article
- Pathogenesis and Clinical Significance of In-Stent Restenosis in Patients with Diabetes.International journal of environmental research and public health · 2021Review
- Inflammation: a putative link between phosphate metabolism and cardiovascular disease.Clinical science (London, England : 1979) · 2021Review
- The Metabolism of Epoxyeicosatrienoic Acids by Soluble Epoxide Hydrolase Is Protective against the Development of Vascular Calcification.International journal of molecular sciences · 2020Article
- Aging-associated genesOncology letters · 2020Article
- Review
- TNFRSF12A and CD38 Contribute to a Vicious Circle for Chronic Obstructive Pulmonary Disease by Engaging Senescence Pathways.Frontiers in cell and developmental biology · 2020Article
- Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcificationComputational and structural biotechnology journal · 2020Article
- A journey from microenvironment to macroenvironment: the role of metaflammation and epigenetic changes in cardiorenal disease.Clinical kidney journal · 2019Article
- A major role of TWEAK/Fn14 axis as a therapeutic target for post-angioplasty restenosis.EBioMedicine · 2019Article
- TRAIL, OPG, and TWEAK in kidney disease: biomarkers or therapeutic targets?Clinical science (London, England : 1979) · 2019Review
- Selenoprotein S inhibits inflammation-induced vascular smooth muscle cell calcification.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular calcification (VC) is associated with increased cardiovascular mortality in aging, chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM) and atherosclerosis. TNF-like weak inducer of apoptosis (TWEAK) recently emerged as a new biomarker for the diagnosis and prognosis of cardiovascular diseases. TWEAK binding to its functional receptor Fn14 was reported to promote several steps of atherosclerotic plaque progression. However, no information is currently available on the role of TWEAK/Fn14 on the development of medial calcification, which is highly prevalent in aging, CKD and T2DM. This study explored the involvement of TWEAK in human vascular smooth muscle cells (h-VSMCs) calcification in vitro. We report that TWEAK binding to Fn14 promotes inorganic phosphate-induced h-VSMCs calcification, favors h-VSMCs osteogenic transition, decreasing acta2 and myh11 and increasing bmp2 mRNA and tissue non-specific alkaline phosphatase (TNAP), and increases MMP9 activity. Blockade of the canonical NFκB pathway reduced by 80% TWEAK pro-calcific properties and decreased osteogenic transition, TNAP and MMP9 activity. Blockade of non-canonical NFκB signaling by a siRNA targeting RelB reduced by 20% TWEAK pro-calcific effects and decreased TWEAK-induced loss of h-VSMCs contractile phenotype and MMP9 activity, without modulating bmp2 mRNA or TNAP activity. Inhibition of ERK1/2 activation by a MAPK kinase inhibitor did not influence TWEAK pro-calcific properties. Our results suggest that TWEAK/Fn14 directly favors inorganic phosphate-induced h-VSMCs calcification by activation of both canonical and non-canonical NFκB pathways. Given the availability of neutralizing anti-TWEAK strategies, our study sheds light on the TWEAK/Fn14 axis as a novel therapeutic target in the prevention of VC.
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