A major fraction of fibronectin present in the extracellular matrix of tissues is plasma-derived
A major fraction of fibronectin present in the extracellular matrix of tissues is plasma-derived
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DOI：
10.1074/jbc.m611315200
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发表时间：
2007-09-21
影响因子：
4.8
通讯作者：
Muro, Andres F.
中科院分区：
文献类型：
--
作者：
Moretti, Federico A.;Chauhan, Anil K.;Muro, Andres F.
在组织细胞外基质中发现的纤维连接蛋白（FN）的起源尚未通过实验确定。先前的研究表明，局部组织的产生和血浆的转移都有贡献，但这种现象的程度尚未得到解决。我们之前已经证明，组成性表达含有额外结构域a的FN （EDA(+)FN）的工程小鼠在血浆和大多数组织中FN水平显著降低。我们发现经修饰产生EDA(+)FN的肝细胞具有正常的细胞外基质FN水平，但分泌较少的可溶性FN。当我们对这些动物进行肝脏特异性edia -外显子删除时，血浆和组织中的FN水平都恢复了。因此，组织FN的重要部分，大约等于组织本身产生的数量，实际上是来自血浆，这表明血浆是组织FN的重要来源。目前的研究结果使人们对血浆FN（可能还有其他血浆蛋白）在调节细胞活动和组织细胞外基质形成过程中的作用的理解减少了一半。
The origin of the fibronectin (FN) found in the extracellular matrix of tissues has not been defined experimentally. Previous studies suggest that there is contribution from both local tissue production and transfer from plasma, but the extent of this phenomenon has not been addressed. We have shown before that engineered mice constitutively expressing extra domain A-containing FN (EDA(+)FN) have a significant decrease of FN levels in plasma and most tissues. We showed that hepatocytes modified to produce EDA(+)FN have normal extracellular matrix-FN levels but secrete less soluble FN. When we performed a liver-specific EDiA-exon deletion in these animals, FN levels were restored both in plasma and tissues. Therefore, an important fraction of tissue FN, approximately an equal amount of that produced by the tissue itself, is actually plasma-derived, suggesting that plasma is an important source of tissue FN. The present results halve potential significance for understanding the contributions of plasma FN, and perhaps other plasma proteins, in the modulation of cellular activities and in the formation of the extracellular matrix of tissues.