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Mgp  -  matrix Gla protein

Rattus norvegicus

Synonyms: MGP, Matrix Gla protein
 
 
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Disease relevance of Mgp

 

High impact information on Mgp

 

Biological context of Mgp

  • Matrix GLA protein modulates branching morphogenesis in fetal rat lung [6].
  • Taken together, the results suggest that MGP plays a role in lung growth and development, likely via temporally and spatially specific interactions with other branching morphogenesis-related proteins to influence growth processes [6].
  • Lung, heart, and kidney express high levels of mRNA for the vitamin K-dependent matrix Gla protein. Implications for the possible functions of matrix Gla protein and for the tissue distribution of the gamma-carboxylase [7].
  • Bone origin of the serum complex of calcium, phosphate, fetuin, and matrix Gla protein: biochemical evidence for the cancellous bone-remodeling compartment [8].
  • We previously described the discovery of a fetuin-matrix Gla protein (MGP)-mineral complex in the serum of rats treated with the bone-active bisphosphonate etidronate and showed that the appearance of this complex in serum correlates with the inhibition of bone mineralization by etidronate [8].
 

Anatomical context of Mgp

  • Recent studies in humans have shown that although MGP mRNA is constitutively expressed by normal vascular smooth muscle cells (VSMCs), it is substantially upregulated in cells adjacent to both medial and intimal calcification [9].
  • Immunohistochemical analysis revealed increased staining for MGP in peripheral mesenchyme surrounding distal epithelial tubules [6].
  • Matrix Gla protein (MGP), a vitamin K-dependent protein known to be synthesized in type II cells, was also found in fetal fibroblasts, where its expression was stimulated by Dex [10].
  • Matrix gamma-carboxyglutamic acid protein (MGP) is a mineral-binding extracellular matrix protein synthesized by vascular smooth muscle cells (VSMCs) and chondrocytes that is thought to be a key regulator of tissue calcification [11].
  • Osteoblasts produce at least three different Gla-containing proteins: osteocalcin, matrix Gla-protein, and protein S. After cellular secretion of these proteins, the main part of each remains bound to the hydroxyapatite matrix in bone, but their function remains unclear [12].
 

Associations of Mgp with chemical compounds

  • Studies in rats and on cultured human VSMCs showing that inhibition of MGP function by warfarin can accelerate spontaneous calcification have emphasized the potential importance of posttranslational processing in determining MGP function [9].
  • The vitamin K-dependent bone protein matrix gamma-carboxyglutamic acid (Gla) protein (MGP) has been identified by radioimmunoassay in the guanidine extract of rat cartilage [13].
  • Treatment with vitamin D alone increased levels of matrix Gla protein, an inhibitor of soft tissue calcification, in the arteries, kidneys, lungs and trachea by 10- to 100-fold, and ibandronate treatment prevented this increase [14].
  • The combination of RA and calcitriol had a synergistic effect on ALP, OP, and especially MGP mRNA expression but significantly reduced the expression of pro-alpha 1(I) collagen mRNA [15].
  • MGP mRNA levels in both osteoblasts and chondrocytes in culture were significantly elevated by 1,25-(OH)2D3 (10(-8) M, 48 h) throughout the time course of cellular growth and differentiation [16].
 

Other interactions of Mgp

 

Analytical, diagnostic and therapeutic context of Mgp

  • Conversely, intraluminal microinjection of anti-MGP antibodies had no effect either on explant growth or MGP expression, supporting the hypothesis that MGP exerts its effects through the mesenchyme [6].
  • Relationship between immunological rejection and matrix GLA protein in cryopreserved vascular allografts [20].
  • In this study we examined the relationship between immunological rejection and MGP in cryopreserved rat aortic grafts after transplantation [20].
  • RESULTS: There was no significant difference in intragraft MGP mRNA levels between fresh and cryopreserved isografts 9 days after transplantation [20].
  • The grafts were retrieved 9 days after transplantation and the intragraft MGP mRNA was measured by a real-time quantitative PCR method [20].

References

  1. Molecular cloning of matrix Gla protein: implications for substrate recognition by the vitamin K-dependent gamma-carboxylase. Price, P.A., Fraser, J.D., Metz-Virca, G. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  2. The warfarin embryopathy: a rat model showing maxillonasal hypoplasia and other skeletal disturbances. Howe, A.M., Webster, W.S. Teratology (1992) [Pubmed]
  3. Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene. Kirfel, J., Kelter, M., Cancela, L.M., Price, P.A., Schüle, R. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  4. Biochemical characterization of the serum fetuin-mineral complex. Price, P.A., Nguyen, T.M., Williamson, M.K. J. Biol. Chem. (2003) [Pubmed]
  5. Discovery of a high molecular weight complex of calcium, phosphate, fetuin, and matrix gamma-carboxyglutamic acid protein in the serum of etidronate-treated rats. Price, P.A., Thomas, G.R., Pardini, A.W., Figueira, W.F., Caputo, J.M., Williamson, M.K. J. Biol. Chem. (2002) [Pubmed]
  6. Matrix GLA protein modulates branching morphogenesis in fetal rat lung. Gilbert, K.A., Rannels, S.R. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  7. Lung, heart, and kidney express high levels of mRNA for the vitamin K-dependent matrix Gla protein. Implications for the possible functions of matrix Gla protein and for the tissue distribution of the gamma-carboxylase. Fraser, J.D., Price, P.A. J. Biol. Chem. (1988) [Pubmed]
  8. Bone origin of the serum complex of calcium, phosphate, fetuin, and matrix Gla protein: biochemical evidence for the cancellous bone-remodeling compartment. Price, P.A., Caputo, J.M., Williamson, M.K. J. Bone Miner. Res. (2002) [Pubmed]
  9. The role of Gla proteins in vascular calcification. Shanahan, C.M., Proudfoot, D., Farzaneh-Far, A., Weissberg, P.L. Crit. Rev. Eukaryot. Gene Expr. (1998) [Pubmed]
  10. Glucocorticoid effects on vitamin K-dependent carboxylase activity and matrix Gla protein expression in rat lung. Gilbert, K.A., Rannels, S.R. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  11. A polymorphism of the human matrix gamma-carboxyglutamic acid protein promoter alters binding of an activating protein-1 complex and is associated with altered transcription and serum levels. Farzaneh-Far, A., Davies, J.D., Braam, L.A., Spronk, H.M., Proudfoot, D., Chan, S.W., O'Shaughnessy, K.M., Weissberg, P.L., Vermeer, C., Shanahan, C.M. J. Biol. Chem. (2001) [Pubmed]
  12. Role of vitamin K in bone metabolism. Vermeer, C., Jie, K.S., Knapen, M.H. Annu. Rev. Nutr. (1995) [Pubmed]
  13. The identification of matrix Gla protein in cartilage. Hale, J.E., Fraser, J.D., Price, P.A. J. Biol. Chem. (1988) [Pubmed]
  14. The amino bisphosphonate ibandronate prevents vitamin D toxicity and inhibits vitamin D-induced calcification of arteries, cartilage, lungs and kidneys in rats. Price, P.A., Buckley, J.R., Williamson, M.K. J. Nutr. (2001) [Pubmed]
  15. Effects of ascorbic acid, calcitriol, and retinoic acid on the differentiation of preosteoblasts. Choong, P.F., Martin, T.J., Ng, K.W. J. Orthop. Res. (1993) [Pubmed]
  16. Developmental expression and hormonal regulation of the rat matrix Gla protein (MGP) gene in chondrogenesis and osteogenesis. Barone, L.M., Owen, T.A., Tassinari, M.S., Bortell, R., Stein, G.S., Lian, J.B. J. Cell. Biochem. (1991) [Pubmed]
  17. Alterations of bone matrix protein mRNA expression in rat aorta in vitro. Hao, H., Hirota, S., Tsukamoto, Y., Imakita, M., Ishibashi-Ueda, H., Yutani, C. Arterioscler. Thromb. Vasc. Biol. (1995) [Pubmed]
  18. Vitamin K-dependent carboxylase: utilization of decarboxylated bone Gla protein and matrix Gla protein as substrates. Engelke, J.A., Hale, J.E., Suttie, J.W., Price, P.A. Biochim. Biophys. Acta (1991) [Pubmed]
  19. Distinct upregulation of extracellular matrix genes in transition from hypertrophy to hypertensive heart failure. Rysä, J., Leskinen, H., Ilves, M., Ruskoaho, H. Hypertension (2005) [Pubmed]
  20. Relationship between immunological rejection and matrix GLA protein in cryopreserved vascular allografts. Kiji, T., Dohi, Y., Nishizaki, K., Sakaguchi, H., Nagasaka, S., Hayata, Y., Yonemasu, K., Taniguchi, S. Transplant. Proc. (2004) [Pubmed]
 
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