Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum
Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum
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DOI：
10.4161/cc.10.11.15681
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发表时间：
2011-06-01
期刊：
影响因子：
4.3
通讯作者：
Le Saux, Olivier
中科院分区：
文献类型：
--
作者：
Brampton, Christopher;Yamaguchi, Yukiko;Le Saux, Olivier
弹性纤维性假黄瘤（PXE）是一种遗传性疾病，其特征是皮肤、眼部和血管组织中的弹性纤维钙化。PXE是由ABCC 6突变引起的，ABCC 6编码ATP驱动的有机阴离子转运蛋白家族的蛋白质。这种转运蛋白不能将其底物分泌到循环中可能是PXE的原因。维生素K作为钙化抑制剂（如基质玻璃蛋白（MGP））羧化的辅助因子，在矿化过程的调节中发挥作用。维生素K前体或缀合形式已被提议作为ABCC 6的潜在底物。我们研究了富含维生素K1或维生素K2（MK 4）的饮食是否可以阻止或减缓Abcc 6（-/-）小鼠的疾病进展。Abcc 6（-/-）小鼠在出生前、3周龄或3月龄时以5或100 mg/kg的维生素K1或MK 4饮食。通过测量小鼠鼻口皮肤一侧的钙含量和对侧的钙进行组织学染色来量化疾病进展。提高饮食中维生素K1或MK 4的含量会增加血清中循环MK 4的浓度。然而，与对照组相比，这种增加并没有显著影响MGP羧化状态或减少其异常丰度、总钙含量或3个处理组的胡须中的病理性钙化。我们的研究结果表明，提高维生素K1或MK 4的饮食摄入量对治疗PXE没有好处，并表明维生素K的可用性可能不是这种病理学的限制因素。
Pseudoxanthoma elasticum (PXE) is a heritable disease characterized by calcified elastic fibers in cutaneous, ocular and vascular tissues. PXE is caused by mutations in ABCC6, which encodes a protein of the ATP-driven organic anion transporter family. The inability of this transporter to secrete its substrate into the circulation is the likely cause of PXE. Vitamin K plays a role in the regulation of mineralization processes as a co-factor in the carboxylation of calcification inhibitors such as Matrix Gla Protein (MGP). Vitamin K precursor or a conjugated form has been proposed as potential substrate(s) for ABCC6. We investigated whether an enriched diet of vitamin K1 or vitamin K2 (MK4) could stop or slow the disease progression in Abcc6(-/-) mice. Abcc6(-/-) mice were placed on a diet of either vitamin K1 or MK4 at 5 or 100 mg/kg at prenatal, 3 weeks or 3 months of age. Disease progression was quantified by measuring the calcium content of one side of the mouse muzzle skin and histological staining for calcium of the opposing side. Raising the vitamin K1 or MK4 content of the diet increased the concentration of circulating MK4 in the serum. However, this increase did not significantly affect the MGP carboxylation status or reduce its abnormal abundance, the total calcium content or the pathologic calcification in the whiskers of the 3 treatment groups compared to controls. Our findings showed that raising the dietary intake of vitamin K1 or MK4 was not beneficial in the treatment of PXE and suggested that the availability of vitamin K may not be a limiting factor in this pathology.