Transglutaminase 2 accelerates vascular calcification in chronic kidney disease

Xuening (Neal) Chen, Kalisha O'Neill, Xianming Chen, Kraiwiporn Kiattisunthorn, Vincent H. Gattone, Sharon Moe

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)191-198
Number of pages8
JournalAmerican Journal of Nephrology
Volume37
Issue number3
DOIs
StatePublished - Apr 2013

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Vascular Calcification
Chronic Renal Insufficiency
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cystamine
Extracellular Matrix
Collagen Type I
Extracellular Matrix Proteins
transglutaminase 2
Thoracic Aorta
Fibronectins
Integrins
Phosphorus
Alkaline Phosphatase
Aorta
Diet
Calcium
Enzymes

Keywords

  • Chronic kidney disease
  • Extracellular matrix-cell interaction
  • Vascular calcification

ASJC Scopus subject areas

  • Nephrology

Cite this

Transglutaminase 2 accelerates vascular calcification in chronic kidney disease. / Chen, Xuening (Neal); O'Neill, Kalisha; Chen, Xianming; Kiattisunthorn, Kraiwiporn; Gattone, Vincent H.; Moe, Sharon.

In: American Journal of Nephrology, Vol. 37, No. 3, 04.2013, p. 191-198.

Research output: Contribution to journalArticle

Chen, Xuening (Neal) ; O'Neill, Kalisha ; Chen, Xianming ; Kiattisunthorn, Kraiwiporn ; Gattone, Vincent H. ; Moe, Sharon. / Transglutaminase 2 accelerates vascular calcification in chronic kidney disease. In: American Journal of Nephrology. 2013 ; Vol. 37, No. 3. pp. 191-198.
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