Osteopontin is synthesized by uterine glands and a 45-kDa cleavage fragment is localized at the uterine-placental interface throughout ovine pregnancy
Osteopontin is synthesized by uterine glands and a 45-kDa cleavage fragment is localized at the uterine-placental interface throughout ovine pregnancy
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DOI：
10.1095/biolreprod.102.013573
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发表时间：
2003-07-01
影响因子：
3.6
通讯作者：
Pfarrer, C
中科院分区：
文献类型：
--
作者：
Johnson, GA;Burghardt, RC;Pfarrer, C
骨桥蛋白（OPN）是一种磷酸化和糖基化的分泌蛋白，存在于各种上皮细胞和生物液体中。在冷冻和解冻或用蛋白酶处理时，天然70-kDa蛋白质产生45-和24-kDa片段。分泌的OPN作为细胞外基质（ECM）蛋白发挥作用，其结合细胞表面受体以介导细胞-细胞粘附、细胞-ECM通信和细胞迁移。在绵羊和人类中，OPN被认为是子宫腺上皮（GE）的分泌产物，其与子宫腔上皮（LE）和孕体滋养外胚层结合以介导孕体附着，这对于在围着床期维持妊娠至关重要。细胞-细胞粘附、通讯和迁移可能在整个妊娠期间子宫和胎盘之间的界面处是重要的，但据我们所知，在绵羊中没有记录到OPN在围着床期之后的子宫内膜和/或胎盘表达。因此，本研究确定了妊娠第25天和第120天之间绵羊子宫中OPN mRNA和蛋白表达的时间和空间变化。在妊娠第40天至第80天之间，总绵羊子宫内膜中的OPN mRNA增加了30倍。原位杂交和免疫荧光分析显示，在整个妊娠过程中，OPN mRNA和蛋白的主要来源是子宫GE。有趣的是，45-kDa形式的OPN在妊娠第120天仅在LE顶面、孕体滋养外胚层和胎盘间区和胎盘区的子宫-胎盘界面沿着检测到，连续且沿着丰富。45-kDa OPN是天然70-kDa OPN的蛋白水解切割片段，并且它是妊娠早期子宫潮红中最丰富的形式。45-kDa OPN比天然70-kDa蛋白更刺激细胞附着和细胞迁移。总的来说，本结果支持以下假设：绵羊OPN是由子宫GE分泌的组织营养菌的组分，其在子宫-胎盘界面处积累以影响绵羊整个妊娠期的母胎相互作用。
Osteopontin (OPN) is a phosphorylated and glycosylated, secreted protein that is present in various epithelial cells and biological fluids. On freezing and thawing or treatment with proteases, the native 70-kDa protein gives rise to 45- and 24-kDa fragments. Secreted OPN functions as an extracellular matrix (ECM) protein that binds cell surface receptors to mediate cell-cell adhesion, cell-ECM communication, and cell migration. In sheep and humans, OPN is proposed to be a secretory product of uterine glandular epithelium (GE) that binds to uterine luminal epithelium (LE) and conceptus trophectoderm to mediate conceptus attachment, which is essential to maintain pregnancy through the peri-implantation period. Cell-cell adhesion, communication, and migration likely are important at the interface between uterus and placenta throughout pregnancy, but to our knowledge, endometrial and/or placental expression of OPN beyond the peri-implantation period has not been documented in sheep. Therefore, the present study determined temporal and spatial alterations in OPN mRNA and protein expression in the ovine uterus between Days 25 and 120 of pregnancy. The OPN mRNA in total ovine endometrium increased 30-fold between Days 40 and 80 of gestation. In situ hybridization and immunofluorescence analyses revealed that the predominant source of OPN mRNA and protein throughout pregnancy was the uterine GE. Interestingly, the 45-kDa form of OPN was detected exclusively, continuously, and abundantly along the apical surface of LE, on conceptus trophectoderm, and along the uterine-placental interface of both interplacentomal and placentomal regions through Day 120 of pregnancy. The 45-kDa OPN is a proteolytic cleavage fragment of the native 70-kDa OPN, and it is the most abundant form in uterine flushes during early pregnancy. The 45-kDa OPN is more stimulatory to cell attachment and cell migration than the native 70-kDa protein. Collectively, the present results support the hypothesis that ovine OPN is a component of histotroph secreted by the uterine GE that accumulates at the uteri ne-placental interface to influence maternal-fetal interactions throughout gestation in sheep.