In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/β-catenin activation

Martínez-Moreno, Julio M.; Muñoz‐Castañeda, Juan R.; Herencia, Carmen; de, Addy Montes; Estepa, J. C.; Canalejo, Rocío; Rodríguez‐Ortiz, María E.; Pérez-Martínez, Pablo; Aguilera–Tejero, Escolástico; Canalejo, Antonio; Rodríguez, Mariano; Almadén, Yolanda

doi:10.1152/ajprenal.00684.2011

Cited by 87 publications

(72 citation statements)

References 64 publications

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“…Trabd2 encodes for a protein that antagonizes the Wnt signaling pathway (Clevers and Nusse 2012). Recent works have shown that Wnt signaling pathway activation can tigger calcification of VSMCs (Martínez-Moreno et al 2012). We also observed a decrease of threhalase gene transcription level.…”

Section: Arsenicsupporting

confidence: 61%

Transcriptome profile analysis reveals specific signatures of pollutants in Atlantic eels

et al. 2014

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Identifying specific effects of contaminants in a multi-stress field context remain a challenge in ecotoxicology. In this context, ''omics'' technologies, by allowing the simultaneous measurement of numerous biological endpoints, could help unravel the in situ toxicity of contaminants. In this study, wild Atlantic eels were sampled in 8 sites presenting a broad contamination gradient in France and Canada. The global hepatic transcriptome of animals was determined by RNA-Seq. In parallel, the contamination level of fish to 8 metals and 25 organic pollutants was determined. Factor analysis for multiple testing was used to identify genes that are most likely to be related to a single factor. Among the variables analyzed, arsenic (As), cadmium (Cd), lindane (c-HCH) and the hepato-somatic index (HSI) were found to be the main factors affecting eel's transcriptome. Genes associated with As exposure were involved in the mechanisms that have been described during As vasculotoxicity in mammals. Genes correlated with Cd were involved in cell cycle and energy metabolism. For c-HCH, genes were involved in lipolysis and cell growth. Genes associated with HSI were involved in protein, lipid and iron metabolisms. Our study proposes specific gene signatures of pollutants and their impacts in fish exposed to multi-stress conditions.

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Section: Arsenicsupporting

confidence: 61%

Transcriptome profile analysis reveals specific signatures of pollutants in Atlantic eels

et al. 2014

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“…It is known that the Wnt/β-catenin pathway plays a key role in the pathogenesis of vascular calcification [23,24], inducing the expression of calcification and osteoblastic markers through the upregulation of Runx2 transcription [11]. To investigate whether high Pi induced vascular calcification via the Wnt/β-catenin pathway, we employed a luciferase reporter system for the Wnt/β-catenin pathway, TOP/FOP-Flash [25].…”

Section: Discussionmentioning

confidence: 99%

High Phosphorus Level Leads to Aortic Calcification via β-Catenin in Chronic Kidney Disease

Sun

et al. 2015

Am J Nephrol

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Aims: Vascular calcification is a risk factor for causing cardiovascular events and has a high prevalence among chronic kidney disease (CKD) patients. However, the molecular mechanism underlying this pathogenic process is still obscure. Methods: Vascular smooth muscle cells (VSMCs) were induced by a concentration of phosphorus (Pi) of 2.5 mM, and were subjected to cell calcification analyses. The effect of high Pi on the Wnt/β-catenin pathway was measured using a TOP/FOP-Flash reporter assay. The transcriptional regulation of β-catenin on PIT1 (a type III sodium-dependent phosphate cotransporter) was confirmed by promoter reporter and chromatin immunoprecipitation assays. The 5/6 nephrectomized rat was used as an in vivo model and was fed a high Pi diet to induce aortic calcification. Serum levels of phosphate, calcium, creatine, and blood urea nitrogen were measured, and abdominal aortic calcification was examined. Results: High Pi induced VSMC calcification, downregulated expression levels of VSMC markers, and upregulated levels of osteogenic markers. High Pi activated the Wnt/β-catenin pathway and β-catenin activity. β-Catenin was involved in the process of high Pi-induced VSMC calcification. Further investigation revealed that β-catenin transcriptionally regulated Pit1, a necessary player in VSMC osteogenic phenotype change and calcification. The in vivo study showed that β-catenin was involved in rat abdominal aortic calcification induced by high Pi. When knockdown expression of β-catenin in the rat model was investigated, we found that aortic calcification was reduced. Conclusion: These results suggest that β-catenin is an important player in high phosphorus level-induced aortic calcification in CKD.

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“…Wnt signaling, which plays a critical role in the commitment of pluripotent mesenchymal cells, is activated during VC [17]. Wnt proteins bind to a coreceptor complex formed by proteins of the frizzled (Fzd) family and lipoprotein receptor related 5/6 proteins (Lrp5/6).…”

Section: Introductionmentioning

confidence: 99%

Vascular Calcification in Chronic Kidney Disease is Induced by Bone Morphogenetic Protein-2 via a Mechanism Involving the Wnt/�-Catenin Pathway

Shu

Zhao

Jin

et al. 2014

Cell Physiol Biochem

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Background: Vascular calcification (VC), in which vascular smooth muscle cells (VSMCs) undergo a phenotypic transformation into osteoblast-like cells, is one of the emergent risk factors for the accelerated atherosclerosis process characteristic of chronic kidney disease (CKD). Phosphate is an important regulator of VC. Methods: The expression of different smooth muscle cell or osteogenesis markers in response to high concentrations of phosphate or exogenous bone morphogenetic protein 2 (BMP-2) was examined by qRT-PCR and western blotting in rat VSMCs. Osteocalcin secretion was measured by radioimmunoassay. Differentiation and calcification of VSMCs were examined by alkaline phosphatase (ALP) activity assay and Alizarin staining. Short hairpin RNA-mediated silencing of β-catenin was performed to examine the involvement of Wnt/β-catenin signaling in VSMC calcification and osteoblastic differentiation induced by high phosphate or BMP-2. Apoptosis was determined by TUNEL assay and immunofluorescence imaging. Results: BMP-2 serum levels were significantly higher in CKD patients than in controls. High phosphate concentrations and BMP-2 induced VSMC apoptosis and upregulated the expression of β-catenin, Msx2, Runx2 and the phosphate cotransporter Pit1, whereas a BMP-2 neutralization antibody reversed these effects. Knockdown of β-catenin abolished the effect of high phosphate and BMP-2 on VSMC apoptosis and calcification. Conclusions: BMP-2 plays a crucial role in calcium deposition in VSMCs and VC in CKD patients via a mechanism involving the Wnt/β-catenin pathway.

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In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/β-catenin activation

Cited by 87 publications

References 64 publications

Transcriptome profile analysis reveals specific signatures of pollutants in Atlantic eels

Transcriptome profile analysis reveals specific signatures of pollutants in Atlantic eels

High Phosphorus Level Leads to Aortic Calcification via β-Catenin in Chronic Kidney Disease

Vascular Calcification in Chronic Kidney Disease is Induced by Bone Morphogenetic Protein-2 via a Mechanism Involving the Wnt/�-Catenin Pathway

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