Ovine osteopontin:: II.: Osteopontin and αvβ3 integrin expression in the uterus and conceptus during the periimplantation period
Ovine osteopontin:: II.: Osteopontin and αvβ3 integrin expression in the uterus and conceptus during the periimplantation period
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DOI：
10.1095/biolreprod61.4.892
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发表时间：
1999-10-01
影响因子：
3.6
通讯作者：
Bazer, FW
中科院分区：
文献类型：
--
作者：
Johnson, GA;Burghardt, RC;Bazer, FW
骨桥蛋白（OPN）是一种70 kda的酸性糖蛋白，可被蛋白酶裂解产生45 kda和24 kda的片段。70-kDa和45-kDa蛋白含有gly - arg - clay - asp - ser （GRGDS）序列，该序列与细胞表面整合素(主要是α （v) β(3)异二聚体）结合，促进细胞间的附着和细胞扩散。在妊娠第17天的子宫内膜细胞质提取物中，用二维（2D） PAGE检测到一个70 kda的酸性蛋白，并用Western blotting鉴定为免疫反应性OPN。通过1D PAGE和Western blot检测子宫内膜提取物的三种免疫反应性OPN蛋白（70、45和24 kDa）。子宫内膜提取物中的OPN蛋白在孕母羊和孕母羊之间没有差异。然而，在第11天至第17天期间，怀孕母羊的子宫冲洗中45 kda的OPN量增加。免疫反应性OPN定位于周期母羊和妊娠母羊的管腔上皮和腺上皮，以及第19天妊娠母羊的滋养外胚层。免疫荧光法在第19天子宫内膜和妊娠期检测α (v)和β(3)整合素。据报道，妊娠早期母羊子宫腺中OPN mRNA增加，宫腔中OPN蛋白的分泌增加。目前的结果表明，OPN蛋白在子宫内膜LE和妊娠滋养外胚层上积累。因此，我们假设黄体酮和/或干扰素-tau诱导子宫上皮OPN的表达、分泌和/或蛋白水解裂解。分泌的OPN可作为滋养外胚层和子宫上α （v) β(3)整合素异二聚体的配体，以1）刺激孕胚滋养外胚层形态的变化，2)诱导腔上皮和滋养外胚层之间的粘连，这是植入和胎盘所必需的。
Osteopontin (OPN) is an acidic 70-kDa glycoprotein that is cleaved by proteases to yield 45-kDa and 24-kDa fragments. The 70-kDa and 45-kDa proteins contain a Gly-Arg-Cly-Asp-Ser (GRGDS) sequence that binds to cell surface integrins (primarily alpha(v)beta(3) heterodimer) to promote cell-cell attachment and cell spreading. A 70-kDa acidic protein was previously detected by two-dimensional (2D) PAGE in Day 17 pregnant endometrial cytosolic extracts using Stainsall and identified as immunoreactive OPN using Western blotting. Three forms of immunoreactive OPN proteins (70, 45, and 24 kDa) were detected by 1D PAGE and Western blot analysis of endometrial extracts. OPN protein in endometrial extracts did not differ between cyclic and pregnant ewes. However, the amount of 45-kDa OPN increased in uterine flushings from pregnant ewes between Days 11 and 17. Immunoreactive OPN was localized to luminal and glandular epithelia of both cyclic and pregnant ewes, and to trophectoderm of Day 19 conceptuses. The alpha(v) and beta(3) integrins were detected on Day 19 endometrium and conceptuses by immunofluorescence. It was reported that OPN mRNA increases in the uterine glands of pregnant ewes and secretion of OPN protein into the uterine lumen increases during early pregnancy. The present results demonstrate accumulation of OPN protein on endometrial LE and conceptus trophectoderm. Therefore, it is hypothesized that progesterone and/or interferon-tau induce expression, secretion and/or proteolytic cleavage of OPN by uterine epithelium. Secreted OPN is then available as ligand for alpha(v)beta(3) integrin heterodimer on trophectoderm and uterus to 1) stimulate changes in morphology of conceptus trophectoderm and 2) induce adhesion between luminal epithelium and trophectoderm essential for implantation and placentation.