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.

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.
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DOI:
10.1016/s0021-9258(18)37912-2
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发表时间:
1988-08
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
J. Fraser;P. Price
J. Fraser;P. Price
中科院分区:
其他
文献类型:
--
作者:
J. Fraser;P. Price

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我们使用了两种依赖维生素K的小分子骨基质蛋白的cDNA探针,即骨GLA蛋白(BGP)和基质GLA蛋白(MGP),以评估这两种蛋白中的任何一种可能是由先前证明具有伽玛-羧基酶活性的各种软组织合成的。在骨中发现了BGP mRNA,但在所测试的任何软组织中均未发现,这一结果强化了血浆BGP是骨代谢的特异性标记物的观点。相反,在所有被检测的大鼠组织中都发现了MGP基因的表达。肺和心脏的MGP mRNA水平是骨骼的10倍,肾脏的MGP mRNA水平是骨骼的5倍。尽管心脏和肾脏中的MGP mRNA水平很高,但这些组织中MGP蛋白的浓度比骨骼低40-500倍。免疫荧光检测肾、肺、心、脾中含有MGP的细胞。在每个组织中,MGP在离散的组织特定细胞类型中被发现。在大多数被测试的软组织中,MGP是第一个被发现合成的具有良好特性的维生素K依赖的羧基酶底物。MGP合成的异常广泛的组织分布表明,MGP的功能并不是结缔组织所特有的,而MGP抗原在高MGP mRNA水平的软组织中的低水平表明,MGP不太可能仅仅依靠其在细胞外基质中的积聚来发挥作用。
We have used cDNA probes for two small vitamin K-dependent bone matrix proteins, bone Gla protein (BGP) and matrix Gla protein (MGP), to evaluate the possibility that either of these proteins might be synthesized by the various soft tissues previously shown to have gamma-carboxylase activity. BGP mRNA was found in bone but not in any of the soft tissues tested, a result which reinforces the view that plasma BGP is a specific marker for bone metabolism. In contrast, MGP mRNA was found in all rat tissues examined. Lung and heart have 10-fold higher levels of MGP mRNA than bone, and kidney has a 5-fold higher level. Despite the high levels of MGP mRNA in heart and kidney, these tissues contain 40-500-fold lower concentrations of MGP protein than bone. Immunofluorescence was used to identify cells that contain MGP in kidney, lung, heart, and spleen. In each tissue, MGP was found in discrete tissue-specific cell types. In most of the soft tissues tested, MGP is the first well characterized substrate for the vitamin K-dependent carboxylase found to be synthesized. The exceptionally broad tissue distribution for MGP synthesis demonstrates that the function of MGP is not specific to connective tissues, and the low levels of MGP antigen in soft tissues with high MGP mRNA levels indicate that MGP is unlikely to act solely by virtue of its accumulation in an extracellular matrix.