title: Transglutaminase 2 accelerates vascular calcification in chronic kidney disease.
abstract: BACKGROUND
  Transglutaminase 2 (TGM2) is a calcium-dependent enzyme that can cross-link nearly all extracellular matrix (ECM) proteins and can facilitate cell-ECM interaction through integrins. Given the importance of the ECM in vascular calcification we tested the hypothesis that increased TGM2 activity may accelerate vascular calcification in chronic kidney disease (CKD).
  
  
  METHODS
  We utilized thoracic aortas and vascular smooth muscle cells (VSMC) from the Cy/+ rat, a model of progressive CKD that develops arterial calcification on a normal phosphorus diet, compared to normal rats.
  
  
  RESULTS
  VSMC isolated from CKD rats had increased expression and activity of TGM2 compared to cells from normal rats. The increased calcification and expression of alkaline phosphatase activity observed in VSMC from CKD rats compared to normal was inhibited in a dose-dependent manner with the TGM inhibitors cystamine and Z006. Matrix vesicles (MV) from CKD rat VSMC also had increased TGM2 expression and the calcification of MV on type I collagen could be inhibited with cystamine and accelerated by exogenous cross-linking of fibronectin or type I collagen with TGM2. Finally, the calcification of aorta rings from CKD rats in ex vivo cultures was inhibited with TGM2 inhibitor.
  
  
  CONCLUSIONS
  These data demonstrate a role of TGM2 in the pathogenesis of vascular calcification in CKD through enhancement of MV-ECM calcification.
authors: Indiana University School of Medicine, Indianapolis, IN 46202, USA. xuechen@iupui.edu
authors: Neal X
authors: NX
authors: Chen
authors: Kalisha
authors: K
authors: O'Neill
authors: Xianming
authors: X
authors: Chen
authors: Kraiwiporn
authors: K
authors: Kiattisunthorn
authors: Vincent H
authors: VH
authors: Gattone
authors: Sharon M
authors: SM
authors: Moe
mesh_terms: D000818:Animals; D001011:Aorta / Q000201:enzymology; D016022:Case-Control Studies; D002478:Cells, Cultured; D004195:Disease Models, Animal; D055354:Exosomes / Q000502:physiology*; D005109:Extracellular Matrix / Q000201:enzymology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000201:enzymology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000201:enzymology*; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D061205:Vascular Calcification / Q000201:enzymology*
chemical_list: D016326:Extracellular Matrix Proteins; C000717609:Tgm2 protein, rat; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins