title: High phosphorus level leads to aortic calcification via β-catenin in chronic kidney disease.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  These results suggest that β-catenin is an important player in high phosphorus level-induced aortic calcification in CKD.
authors: Department of Nephrology, The First Hospital of China Medical University, ShenYang, LiaoNing, China.
authors: Li
authors: L
authors: Yao
authors: Yi-Ting
authors: YT
authors: Sun
authors: Wei
authors: W
authors: Sun
authors: Tian-Hua
authors: TH
authors: Xu
authors: Chuang
authors: C
authors: Ren
authors: Xing
authors: X
authors: Fan
authors: Li
authors: L
authors: Sun
authors: Lin-Lin
authors: LL
authors: Liu
authors: Jiang-Min
authors: JM
authors: Feng
authors: Jian-Fei
authors: JF
authors: Ma
authors: Li-Ning
authors: LN
authors: Wang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001011:Aorta; D001806:Blood Urea Nitrogen; D002118:Calcium / Q000097:blood; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D003401:Creatine / Q000097:blood; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009392:Nephrectomy; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010758:Phosphorus / Q000494:pharmacology*; D016226:Phosphorus, Dietary / Q000378:metabolism; D010955:Plasmalogens / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000235:genetics / Q000378:metabolism; D061205:Vascular Calcification / Q000209:etiology / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D002118:Calcium; D050659:Core Binding Factor Alpha 1 Subunit; D003401:Creatine; D018398:Homeodomain Proteins; D053495:Osteopontin; D010758:Phosphorus; D016226:Phosphorus, Dietary; D010955:Plasmalogens; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D051176:beta Catenin; C084119:MSX2 protein; C493717:Runx2 protein, rat; C498862:Acta2 protein, rat