Publication: Transglutaminase 2 accelerates vascular calcification in chronic kidney disease
Issued Date
2013-04-01
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ISSN
14219670
02508095
02508095
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2-s2.0-84874606745
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Mahidol University
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SCOPUS
Bibliographic Citation
American Journal of Nephrology. Vol.37, No.3 (2013), 191-198
Suggested Citation
Neal X. Chen, Kalisha O'Neill, Xianming Chen, Kraiwiporn Kiattisunthorn, Vincent H. Gattone, Sharon M. Moe Transglutaminase 2 accelerates vascular calcification in chronic kidney disease. American Journal of Nephrology. Vol.37, No.3 (2013), 191-198. doi:10.1159/000347031 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/32414
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Title
Transglutaminase 2 accelerates vascular calcification in chronic kidney disease
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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. Conclusion: These data demonstrate a role of TGM2 in the pathogenesis of vascular calcification in CKD through enhancement of MV-ECM calcification. Copyright © 2013 S. Karger AG, Basel.