Matrix Gla Protein and Alkaline Phosphatase Are Differently Modulated in Human Dermal Fibroblasts from PXE Patients and Controls
Matrix Gla Protein and Alkaline Phosphatase Are Differently Modulated in Human Dermal Fibroblasts from PXE Patients and Controls
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DOI：
10.1038/jid.2012.460
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发表时间：
2013-04-01
影响因子：
6.5
通讯作者：
Quaglino, Daniela
中科院分区：
文献类型：
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作者：
Boraldi, Federica;Annovi, Giulia;Quaglino, Daniela
弹性假黄瘤 (PXE) 中弹性纤维的矿化与羧化基质 gla 蛋白 (MGP) 水平低有关，很可能是维生素 K (vit K) 可用性降低的结果。出乎意料的是，维生素 K 补充剂并未对 PXE 动物模型中的软结缔组织矿化产生有益影响。为了了解补充维生素 K 的效果并试图干扰导致 PXE 矿化软结缔组织内钙和磷酸盐积累的途径，我们对从对照受试者和 PXE 患者中分离的真皮成纤维细胞进行了体外研究。细胞在标准条件下和钙化培养基 (CM) 中培养，并存在维生素 K1 和 K2 或左旋咪唑（一种碱性磷酸酶 (ALP) 抑制剂）。对照和 PXE 成纤维细胞的特征是 vit K1 和 vit K2 的剂量依赖性吸收相似，从而促进所有细胞系中总蛋白羧化的显着增加。然而，PXE 成纤维细胞中的 MGP 羧化仍然少得多。有趣的是，PXE 成纤维细胞表现出显着更高的 ALP 活性。一致地，CM 中长期培养物在体外诱导的矿化过程似乎不受 vit K 的影响，而它被左旋咪唑消除。皮肤病学研究杂志 (2013) 133, 946-954; doi：10.1038/jid.2012.460； 2012 年 12 月 6 日在线发布
Mineralization of elastic fibers in pseudoxanthoma elasticum (PXE) has been associated with low levels of carboxylated matrix gla protein (MGP), most likely as a consequence of reduced vitamin K (vit K) availability. Unexpectedly, vit K supplementation does not exert beneficial effects on soft connective tissue mineralization in the PXE animal model. To understand the effects of vit K supplementation and in the attempt to interfere with pathways leading to the accumulation of calcium and phosphate within PXE-mineralized soft connective tissues, we have conducted in vitro studies on dermal fibroblasts isolated from control subjects and from PXE patients. Cells were cultured in standard conditions and in calcifying medium (CM) in the presence of vit K1 and K2, or levamisole, an alkaline phosphatase (ALP) inhibitor. Control and PXE fibroblasts were characterized by a similar dose-dependent uptake of both vit K1 and vit K2, thus promoting a significant increase of total protein carboxylation in all cell lines. Nevertheless, MGP carboxylation remained much less in PXE fibroblasts. Interestingly, PXE fibroblasts exhibited a significantly higher ALP activity Consistently, the mineralization process induced in vitro by a long-term culture in CM appeared unaffected by vit K, whereas it was abolished by levamisole. Journal of Investigative Dermatology (2013) 133, 946-954; doi:10.1038/jid.2012.460; published online 6 December 2012