Lp3/Hapln3, a novel link protein that co-localizes with versican and is coordinately up-regulated by platelet-derived growth factor in arterial smooth muscle cells

Lp3/Hapln3, a novel link protein that co-localizes with versican and is coordinately up-regulated by platelet-derived growth factor in arterial smooth muscle cells
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DOI:
10.1016/j.matbio.2004.07.001
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发表时间:
2004-08-01
期刊:
影响因子:
6.9
通讯作者:
Ninomiya, Y
Ninomiya, Y
中科院分区:
生物学1区
文献类型:
--
作者:
Ogawa, H;Oohashi, T;Ninomiya, Y

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连接蛋白(Link Proteins,LP)属于连接模块超家族,其可以稳定和增强凝集素与透明质酸的结合。我们在这里报告的一个新的大鼠连接蛋白基因(Lp 3/Hapln 3)的鉴定和表征。推导出的蛋白质序列共享典型的模块化元件的连接蛋白,并有一个估计的质量为39 kDa。对大鼠基因组DNA序列的检查显示,Lp 3/Hapln 3和聚集蛋白聚糖基因在染色体1 q31上配对。另一个LP基因和凝集素基因也在不同的位点配对,就像它们在人类和小鼠基因组中一样。免疫组化显示Lp 3/Hapln 3在血管壁和胃肠道平滑肌组织中有明显表达。进一步的比较研究表明,Lp 3/Hapln 3与多功能蛋白聚糖在血管平滑肌细胞周围而不是内皮细胞周围有很好的共定位。在体外实验中,使用原代培养的大鼠动脉平滑肌细胞(ASMCs)证明了协调上调Lp 3/Hapln 3和多功能蛋白聚糖血小板衍生生长因子(PDGF)。这些数据得到了小鼠机械性血管损伤模型体内研究的支持。总之,我们的研究结果表明,Lp 3/Hapln 3参与,与多功能蛋白聚糖和透明质酸,在血管平滑肌细胞的细胞周围基质的形成。(C)2004年Elsevier B. V./国际矩阵生物学学会。All rights reserved.
Link proteins (LPs) belong to the link-module superfamily, which can stabilize and enhance the binding of lecticans to hyaluronan. We report here the identification and characterization of a novel rat link protein gene (Lp3/Hapln3). The deduced protein sequence shares the typical modular elements of link proteins and has an estimated mass of 39 kDa. Examination of the rat genomic DNA sequence revealed that Lp3/ Hapln3 and aggrecan genes were paired on chromosome 1q31. Another LP gene and the lectican gene were also paired at a different locus, as they are in the human and mouse genomes. Immunohistochemical analysis showed the prominent expression of Lp3/Hapln3 in the smooth muscle tissues of the vascular wall and gastrointestinal tract. Further comparative studies revealed that Lp3/Hapln3 was well co-localized with versican around the smooth muscle cells of blood vessels but not around endothelial cells. In vitro experiments using primary cultured rat arterial smooth muscle cells (ASMCs) demonstrated the coordinated up-regulation of Lp3/Hapln3 and versican by platelet-derived growth factor (PDGF). These data were supported by in vivo studies of a mechanical vascular injury model in mice. Altogether, our results suggest that Lp3/Hapln3 is involved, together with versican and hyaluronan, in the formation of the pericellular matrix of vascular smooth muscle cells. (C) 2004 Elsevier B.V./International Society of Matrix Biology. All rights reserved.