Physiological role of implantation-associated factor Mac25 and the molecular mechanisms of implantation

着床相关因子Mac25的生理作用及着床的分子机制

基本信息

批准号：
13470355
负责人：
KOGO Hiroshi
金额：
$ 8.77万
依托单位：
Tokyo University of Pharmacy and Life Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470355/
关键词：
Implantation mac25 Endometrium

项目摘要

Mac25 (insulin-like growth factor binding protein-related protein 1) is highly expressed in the rat uterus around the time of implantation. We determined the peri-implantation localization of Mac25 mRNA and assessed the effects of recombinant Mac25 on the proliferative and prostacyclin (PGI_2)-producing abilities of cultured endometrial cells early in pregnancy. Mac25 mRNA was detected at high levels in endometrial stromal cells close to the smooth muscle of inter-implantation sites around the time of implantation but absent from decidual zones surrounding the embryo. Differential uterine Mac25 expression was also recognized in the delayed implanting pregnant model, but the level of mRNA decreased as decidual tissues formed in the decidualization model. Recombinant Mac25 inhibited the proliferation of endometrial stromal cells in vitro and arrested them in the G1 phase of the cell cycle. Furthermore, Mac25 significantly stimulated PGI_2 synthesis and cyclooxygenase-2 mRNA expression in myometrial cells, both of which are essential molecules for successful implantation. We constructed a recombinant adenovirus vector encoding Mac25 (Ad-mac) and transfected it to cultured uterine cells derived from early pregnant rats to know bioactivities of Mac25 in the uterus. Ad-mac infection caused increases in Mac25 protein detected in culture media within 72h. Overexpression of Mac25 enhanced expressions for cyclooxygenase-2 and prostaglandin E_2 syntheses mRNAs. These data suggest that Mac25 is an implantation-associated protein and that it modulates the proliferation of rat uterine cells and their production of PGI_2 during the peri-implantation period.

MAC25（胰岛素样生长因子结合蛋白相关蛋白1）在植入时在大鼠子宫中高度表达。我们确定了MAC25 mRNA的植入周期性定位，并评估了重组MAC25对妊娠早期培养子宫内膜细胞的产生能力的增殖和前列环蛋白（PGI_2）的影响。在植入时间附近的子宫基质细胞中检测到MAC25 mRNA，靠近植入部位的平滑肌，但在胚胎周围的can骨区域中不存在。在延迟的植入怀孕模型中也识别出差异子宫MAC25表达，但mRNA的水平降低，因为在deciDualization模型中形成的ni缩组织。重组MAC25在体外抑制了子宫内膜基质细胞的增殖，并在细胞周期的G1阶段将其捕捉。此外，MAC25显着刺激了PGI_2合成和肌层细胞中的环氧酶-2 mRNA表达，这两种表达都是成功植入的必不可少的分子。我们构建了编码MAC25（AD-MAC）的重组腺病毒载体，并将其转染到源自早期孕妇大鼠的培养的子宫细胞中，以了解子宫中MAC25的生物活性。 AD-MAC感染导致在72H内检测到的MAC25蛋白质的增加。 MAC25增强表达式环氧合酶-2和前列腺素E_2合成mRNA的过表达。这些数据表明MAC25是一种与植入相关的蛋白质，它调节大鼠子宫细胞的增殖及其在植入周期期间的PGI_2产生。