Human pregnancy specific beta-1-glycoprotein 1 (PSG1) has a potential role in placental vascular morphogenesis.
Human pregnancy specific beta-1-glycoprotein 1 (PSG1) has a potential role in placental vascular morphogenesis.
复制标题
DOI：
10.1095/biolreprod.109.082412
复制
发表时间：
2010-07
影响因子：
3.6
通讯作者：
Dveksler GS
中科院分区：
文献类型：
--
作者：
Ha CT;Wu JA;Irmak S;Lisboa FA;Dizon AM;Warren JW;Ergun S;Dveksler GS
以前的研究表明，人类妊娠特异的β-1-糖蛋白(PSGs)在妊娠期间起到免疫调节作用；然而，PSGs的其他可能功能仍有待探索。我们观察到PSGs诱导转化生长因子β1(TGFB1)，在其多种功能中，它抑制T细胞功能并具有促血管生成特性。PSG1是母体血清中含量最丰富的PSG，本研究探讨了PSG1作为促血管生成生长因子的可能诱导剂的作用，该因子在母胎界面血管系统的建立中起重要作用。为此，我们检测了PSG1处理后几种细胞中的TGFB1、血管内皮生长因子(VEGFs)A和C以及胎盘生长因子(PGF)的蛋白水平。此外，还进行了管道形成和伤口愈合试验，以研究PSG1与内皮细胞之间可能的直接相互作用。PSG1诱导人单核细胞、巨噬细胞和两种人绒毛外滋养层细胞系TGFB1和VEGFA表达上调。我们没有观察到PSG1在任何被测试的细胞中诱导VEGFC或PGF。PSG1处理可在VEGFA存在和不存在的情况下形成内皮管。用定点突变的方法定位PSG1功能活性所需的N-结构域的重要区域。我们发现，以前认为PSG与细胞结合所需的第95位天冬氨酸对PSG1的活性并不是必需的，但在N-结构域中形成盐桥的氨基酸对PSG1的功能是必不可少的。
Previous studies suggest that human pregnancy specific beta-1-glycoproteins (PSGs) play immunomodulatory roles during pregnancy; however, other possible functions of PSGs have yet to be explored. We have observed that PSGs induce transforming growth factor beta 1 (TGFB1), which among its other diverse functions inhibits T-cell function and has proangiogenic properties. The present study investigates a potential role for PSG1, the most abundant PSG in maternal serum, as a possible inducer of proangiogenic growth factors known to play an important role in establishment of the vasculature at the maternal-fetal interface. To this end, we measured TGFB1, vascular endothelial growth factors (VEGFs) A and C, and placental growth factor (PGF) protein levels in several cell types after PSG1 treatment. In addition, tube formation and wound healing assays were performed to investigate a possible direct interaction between PSG1 and endothelial cells. PSG1 induced up-regulation of both TGFB1 and VEGFA in human monocytes, macrophages, and two human extravillous trophoblast cell lines. We did not observe induction of VEGFC or PGF by PSG1 in any of the cells tested. PSG1 treatment resulted in endothelial tube formation in the presence and absence of VEGFA. Site-directed mutagenesis was performed to map the essential regions within the N-domain of PSG1 required for functional activity. We found that the aspartic acid at position 95, previously believed to be required for binding of PSGs to cells, is not required for PSG1 activity but that the amino acids implicated in the formation of a salt bridge within the N-domain are essential for PSG1 function.
登录
查看更多内容
影响因子：
4
作者：
Clark, DE;Smith, SK;Charnock-Jones, DS
通讯作者：
Charnock-Jones, DS
影响因子：
16
作者：
Ergün, S;Kilic, N;Wagener, C
通讯作者：
Wagener, C
影响因子：
15.9
作者：
Horst, Andrea Kristina;Ito, Wulf D.;Wagener, Christoph
通讯作者：
Wagener, Christoph
影响因子：
3.8
作者：
Mayhew, TM
通讯作者：
Mayhew, TM
DOI：
10.1111/j.1600-0897.2007.00573.x
发表时间：
2008-03-01
影响因子：
3.6
作者：
Ha, Cam T.;Waterhouse, Roseann;Dveksler, Gabriela S.
通讯作者：
Dveksler, Gabriela S.