The Role of GRP and MGP in the Development of Non-Hemorrhagic VKCFD1 Phenotypes
Vitamin K dependent coagulation factor deficiency type 1 (VKCFD1) is a rare hereditary bleeding disorder caused by mutations in γ-Glutamyl carboxylase (<i>GGCX</i>) gene. The GGCX enzyme catalyzes the γ-carboxylation of 15 different vitamin K dependent (VKD) proteins, which have function...
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| author | Suvoshree Ghosh Johannes Oldenburg Katrin J. Czogalla-Nitsche |
| author_facet | Suvoshree Ghosh Johannes Oldenburg Katrin J. Czogalla-Nitsche |
| author_sort | Suvoshree Ghosh |
| collection | DOAJ |
| description | Vitamin K dependent coagulation factor deficiency type 1 (VKCFD1) is a rare hereditary bleeding disorder caused by mutations in γ-Glutamyl carboxylase (<i>GGCX</i>) gene. The GGCX enzyme catalyzes the γ-carboxylation of 15 different vitamin K dependent (VKD) proteins, which have function in blood coagulation, calcification, and cell signaling. Therefore, in addition to bleedings, some VKCFD1 patients develop diverse non-hemorrhagic phenotypes such as skin hyper-laxity, skeletal dysmorphologies, and/or cardiac defects. Recent studies showed that <i>GGCX</i> mutations differentially effect γ-carboxylation of VKD proteins, where clotting factors are sufficiently γ-carboxylated, but not certain non-hemostatic VKD proteins. This could be one reason for the development of diverse phenotypes. The major manifestation of non-hemorrhagic phenotypes in VKCFD1 patients are mineralization defects. Therefore, the mechanism of regulation of calcification by specific VKD proteins as matrix Gla protein (MGP) and Gla-rich protein (GRP) in physiological and pathological conditions is of high interest. This will also help to understand the patho-mechanism of VKCFD1 phenotypes and to deduce new treatment strategies. In the present review article, we have summarized the recent findings on the function of GRP and MGP and how these proteins influence the development of non-hemorrhagic phenotypes in VKCFD1 patients. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:18:16Z |
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| spelling | doaj.art-985bcb72cae441c5be84addbf2756c482023-11-23T14:04:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-0123279810.3390/ijms23020798The Role of GRP and MGP in the Development of Non-Hemorrhagic VKCFD1 PhenotypesSuvoshree Ghosh0Johannes Oldenburg1Katrin J. Czogalla-Nitsche2Institute of Experimental Haematology and Transfusion Medicine, Venusberg Campus 1, University Clinic Bonn, 53127 Bonn, GermanyInstitute of Experimental Haematology and Transfusion Medicine, Venusberg Campus 1, University Clinic Bonn, 53127 Bonn, GermanyInstitute of Experimental Haematology and Transfusion Medicine, Venusberg Campus 1, University Clinic Bonn, 53127 Bonn, GermanyVitamin K dependent coagulation factor deficiency type 1 (VKCFD1) is a rare hereditary bleeding disorder caused by mutations in γ-Glutamyl carboxylase (<i>GGCX</i>) gene. The GGCX enzyme catalyzes the γ-carboxylation of 15 different vitamin K dependent (VKD) proteins, which have function in blood coagulation, calcification, and cell signaling. Therefore, in addition to bleedings, some VKCFD1 patients develop diverse non-hemorrhagic phenotypes such as skin hyper-laxity, skeletal dysmorphologies, and/or cardiac defects. Recent studies showed that <i>GGCX</i> mutations differentially effect γ-carboxylation of VKD proteins, where clotting factors are sufficiently γ-carboxylated, but not certain non-hemostatic VKD proteins. This could be one reason for the development of diverse phenotypes. The major manifestation of non-hemorrhagic phenotypes in VKCFD1 patients are mineralization defects. Therefore, the mechanism of regulation of calcification by specific VKD proteins as matrix Gla protein (MGP) and Gla-rich protein (GRP) in physiological and pathological conditions is of high interest. This will also help to understand the patho-mechanism of VKCFD1 phenotypes and to deduce new treatment strategies. In the present review article, we have summarized the recent findings on the function of GRP and MGP and how these proteins influence the development of non-hemorrhagic phenotypes in VKCFD1 patients.https://www.mdpi.com/1422-0067/23/2/798VKCFD1GGCXGRP/UCMAMGP |
| spellingShingle | Suvoshree Ghosh Johannes Oldenburg Katrin J. Czogalla-Nitsche The Role of GRP and MGP in the Development of Non-Hemorrhagic VKCFD1 Phenotypes International Journal of Molecular Sciences VKCFD1 GGCX GRP/UCMA MGP |
| title | The Role of GRP and MGP in the Development of Non-Hemorrhagic VKCFD1 Phenotypes |
| title_full | The Role of GRP and MGP in the Development of Non-Hemorrhagic VKCFD1 Phenotypes |
| title_fullStr | The Role of GRP and MGP in the Development of Non-Hemorrhagic VKCFD1 Phenotypes |
| title_full_unstemmed | The Role of GRP and MGP in the Development of Non-Hemorrhagic VKCFD1 Phenotypes |
| title_short | The Role of GRP and MGP in the Development of Non-Hemorrhagic VKCFD1 Phenotypes |
| title_sort | role of grp and mgp in the development of non hemorrhagic vkcfd1 phenotypes |
| topic | VKCFD1 GGCX GRP/UCMA MGP |
| url | https://www.mdpi.com/1422-0067/23/2/798 |
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