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

• 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

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.

Mac 25（胰岛素样生长因子结合蛋白相关蛋白1）在着床前后的大鼠子宫中高度表达。我们测定了Mac 25 mRNA在着床周围的定位，并评估了重组Mac 25对妊娠早期培养的子宫内膜细胞增殖和前列环素（PGI_2）产生能力的影响。Mac 25 mRNA在靠近着床间部位平滑肌的子宫内膜基质细胞中以高水平检测到，但在胚胎周围的蜕膜区不存在。在延迟着床妊娠模型中，子宫Mac 25的表达也存在差异，但在蜕膜化模型中，随着蜕膜组织的形成，其mRNA水平降低。重组Mac 25在体外抑制子宫内膜间质细胞的增殖，并将其阻滞在细胞周期的G1期。此外，Mac 25还能显著促进子宫肌层细胞PGI_2的合成和COX-2 mRNA的表达，这两种分子都是着床成功的重要分子。我们构建了Mac 25重组腺病毒载体（Ad-mac），并将其转染到体外培养的早孕大鼠子宫细胞中，以了解Mac 25在子宫中的生物学活性。Ad mac感染后72 h内，培养基中Mac 25蛋白含量明显增加。Mac 25的过表达促进环氧合酶-2和前列腺素E_2合成mRNA的表达。提示Mac 25是一种着床相关蛋白，在围着床期调节大鼠子宫细胞的增殖和PGI_2的产生。

项目成果

Tamura K, Hara T (others 3 persons), Kogo H.: "Enhanced expression of uterine stathmin during the process of implantation and decidualization in rats."Endocrinology. 144. 1464-1473 (2003)

Tamura K、Hara T（其他 3 人）、Kogo H.：“大鼠着床和蜕膜化过程中子宫 stathmin 的表达增强。”内分泌学。

K.Tamura, T.Hara 他3名, H.Kogo.: "Enhanced expression of uterine stathmin during the process of implantation and decidualization in rats."Endocrinology. 144. 1464-1473 (2003)

K.Tamura、T.Hara 和其他 3 人，H.Kogo.：“大鼠着床和蜕膜化过程中子宫 stathmin 的表达增强。”内分泌学。144. 1464-1473 (2003)

K Tamura, T.Hara, 他 3名, H.Kogo: "Enhanced expression of uterine stathmin during the process of implantation and decidualization in rats."Endocrinology. 144. 1464-1473 (2003)

K Tamura、T.Hara 和其他 3 人，H.Kogo：“大鼠着床和蜕膜化过程中子宫 stathmin 的表达增强。”内分泌学 144. 1464-1473 (2003)