Ovarian membrane-type matrix metalloproteinases: induction of MMP14 and MMP16 during the periovulatory period in the rat, macaque, and human.
Ovarian membrane-type matrix metalloproteinases: induction of MMP14 and MMP16 during the periovulatory period in the rat, macaque, and human.
复制标题
卵巢膜型基质金属蛋白酶：大鼠、猕猴和人类排卵期期间 MMP14 和 MMP16 的诱导。
DOI：
10.1095/biolreprod.113.115717
复制
发表时间：
2014
影响因子：
3.6
通讯作者：
CurryJr,ThomasE
中科院分区：
文献类型：
--
作者：
Puttabyatappa,Muraly;Jacot,TerryA;Al-Alem,LinahF;Rosewell,KatherineL;Duffy,DianeM;Brännström,Mats;CurryJr,ThomasE
卵泡内蛋白分解活性的增加会导致排卵事件。令人惊讶的是，膜型基质金属蛋白酶(MT-MMPs)是一种固定在细胞表面的独特的蛋白酶，其排卵期表达谱尚未被广泛研究。研究了MT-MMPs在具有良好特征的大鼠和猕猴排卵期模型以及自然周期妇女排卵期的卵巢组织中的表达情况。在已知的6种MT-MMPs中，给予人绒毛膜促性腺激素(HCG)后，Mmp14、Mmp16和Mmp25mRNA的表达增加。在人颗粒细胞中，经hCG处理后，MMP14和MMP16的mRNA表达增加。相反，人卵泡膜细胞中MMP16和MMP25的mRNA水平在排卵前没有变化，但在排卵后下降。在猕猴颗粒细胞中，hCG可增加MMP16的mRNA，但不能增加MMP14的表达。免疫印迹显示MMP14和MMP16蛋白水平升高，与其mRNA表达相似。在猕猴颗粒细胞中，只有活性形式的MMP14蛋白在hCG后增加，与其mRNA或原蛋白不同。免疫组织化学显示，MMP14和MMP16均定位于大鼠和人不同类型的卵巢细胞。HCG处理后，颗粒细胞和膜细胞中MMP14和MMP16蛋白呈强烈的免疫反应。目前的研究表明，在排卵卵泡中给予hCG可增加MMP14和MMP16的表达，表明这些MMPs在大鼠、猕猴和人类中是保守的。这些发现提示MT-MMPs可能在促进排卵和将排卵卵泡重塑到黄体中起重要作用。
An intrafollicular increase in proteolytic activity drives ovulatory events. Surprisingly, the periovulatory expression profile of the membrane-type matrix metalloproteinases (MT-MMPs), unique proteases anchored to the cell surface, has not been extensively examined. Expression profiles of the MT-MMPs were investigated in ovarian tissue from well-characterized rat and macaque periovulatory models and naturally cycling women across the periovulatory period. Among the six known MT-MMPs, mRNA expression ofMmp14,Mmp16,andMmp25was increased after human chorionic gonadotropin (hCG) administration in rats. In human granulosa cells, mRNA expression ofMMP14andMMP16increased following hCG treatment. In contrast, mRNA levels ofMMP16andMMP25in human theca cells were unchanged before ovulation but declined by the postovulatory stage. In macaque granulosa cells, hCG increased mRNA forMMP16but notMMP14. Immunoblotting showed that protein levels of MMP14 and MMP16 in rats increased, similar to their mRNA expression. In macaque granulosa cells, only the active form of the MMP14 protein increased after hCG, unlike its mRNA or the proprotein. By immunohistochemistry, both MMP14 and MMP16 localized to the different ovarian cell types in rats and humans. Treatment with hCG resulted in intense immunoreactivity of MMP14 and MMP16 proteins in the granulosa and theca cells. The present study shows that MMP14 and MMP16 are increased by hCG administration in the ovulating follicle, demonstrating that these MMPs are conserved among rats, macaques, and humans. These findings suggest that MT-MMPs could have an important role in promoting ovulation and remodeling of the ovulated follicle into the corpus luteum.