Disease relevance of Mgp

• We have used antibodies raised against MGP and oligonucleotide probes to screen a lambda gt11 cDNA library constructed from the rat osteosarcoma cells (line ROS 17/2) that had been pretreated with 1 alpha,25-dihydroxyvitamin D3 [1].
• It is proposed that (1) the facial features of the human warfarin embryopathy are caused by reduced growth of the embryonic nasal septum, and (2) the septal growth retardation occurs because the warfarin-induced extrahepatic vitamin K deficiency prevents the normal formation of the vitamin K-dependent matrix gla protein in the embryo [2].

High impact information on Mgp

• Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene [3].
• Molecular cloning of matrix Gla protein: implications for substrate recognition by the vitamin K-dependent gamma-carboxylase [1].
• Matrix Gla protein (MGP), a low molecular weight protein found in bone, dentin, and cartilage, contains 5 residues of the vitamin K-dependent amino acid gamma-carboxyglutamic acid (Gla) [1].
• This 24-kDa protein is similar in domain structure to fetuin and, like fetuin and MGP, contains several residues of phosphoserine and accumulates in bone [4].
• Treatment with the vitamin K-antagonist warfarin prevents the increase in serum MGP after etidronate injection, which shows that the increase in serum MGP is due to new synthesis and that the gamma-carboxylation of MGP is necessary for its binding to the serum mineral complex [5].

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

• Similarly, antifibronectin antibody treatment resulted in explant dilation and reduced MGP expression, providing evidence for an interaction with MGP and fibronectin [6].
• We examined the expression of matrix Gla protein (MGP), osteopontin (OPN), and osteonectin (ON) mRNAs in aortic rings excised from 3-month-, 10-month-, and 2-week-old rats during 72-hour incubations in serum-free media [17].
• The ability of des-gamma-carboxy bone Gla protein (dBGP) and des-gamma-carboxy matrix Gla protein (dMGP) to act as substrates for the rat liver vitamin K-dependent carboxylase has been investigated [18].
• The microarray analysis also revealed differential gene expression of several novel factors, such as thrombospondin-4 and matrix Gla protein, as well as unknown expressed sequence tags [19].

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