Expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and its related extracellular matrix degrading enzymes in the endometrium during estrous cycle and early gestation in cattle
Expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and its related extracellular matrix degrading enzymes in the endometrium during estrous cycle and early gestation in cattle
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DOI：
10.1186/1477-7827-8-60
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发表时间：
2010-06-11
影响因子：
4.4
通讯作者：
Hashizume, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Mishra, Birendra;Kizaki, Keiichiro;Hashizume, Kazuyoshi
背景：细胞外基质金属蛋白酶诱导剂（EMMPRIN）通过细胞-细胞和细胞-基质相互作用调节多种涉及细胞行为调节的生物学功能。根据其多种功能，我们推测EMMPRIN可能在奶牛子宫内膜重塑和妊娠建立中发挥重要作用。方法：本研究取周期奶牛排卵前、排卵后和发情周期中期的子宫内膜组织；以及妊娠第19天至35天的孕妇子宫内膜组织。采用RT-PCR、qPCR和原位杂交分析mRNA表达，免疫组织化学和western blot分析蛋白表达。结果：EMMPRIN mRNA在孕周和孕周子宫内膜均有表达，且妊娠第35天EMMPRIN mRNA在孕周子宫内膜中的表达明显高于孕周子宫内膜。Western blot分析发现，在培养的牛上皮细胞和BT-1细胞中分别检测到约65kda和约51kda的条带。原位杂交和免疫组织化学数据显示，EMMPRIN主要表达于子宫腔上皮和腺上皮，在妊娠第19天呈强染色。妊娠第19天，子宫腔上皮EMMPRIN mRNA的表达较发情周期中期有所下降，妊娠第30天，胎盘部位EMMPRIN mRNA的表达略有增加。基质金属蛋白酶-2 （matrix metalloproteinase-2, MMP-2）和MMP-14 mRNA主要在基质中表达，在妊娠第19天表达量下降，但EMMPRIN在妊娠第30天胎盘部位也有表达。MMP-1或-9 mRNA的表达极低，低于周期和妊娠子宫内膜的检测限。结论：来自管腔上皮的EMMPRIN可能调节基质MMP-2和-14的表达，提示其在胚胎与管腔上皮的黏附融合过程中直接通过组织的生理重塑和发育过程，以及/或刺激MMPs补偿子宫内膜功能中发挥重要作用。
Background: Extracellular matrix metalloproteinase inducer (EMMPRIN) regulates several biological functions involving the modulation of cell behaviors via cell-cell and cell-matrix interactions. According to its diverse functions, we hypothesized that EMMPRIN may play an important role in endometrial remodeling and establishment of pregnancy in cow.Methods: In this study, endometrial tissues from the cyclic cows during before ovulation, after ovulation and middle of estrous cycle; and pregnant endometrial tissues from Day 19 to 35 of gestation have been used. Expression of mRNA was analyzed by RT-PCR, qPCR and in situ hybridization whereas protein expression by immunohistochemistry and western blot analysis.Results: EMMPRIN mRNA was expressed in both cyclic and pregnant endometrium and significantly higher in the endometrium at Day 35 of gestation than the cyclic endometrium. In Western blot analysis, an approximately 65 kDa band was detected in the endometrium, and approximately 51 kDa in the cultured bovine epithelial cells and BT-1 cells, respectively. Both in situ hybridization and immunohistochemistry data showed that EMMPRIN was primarily expressed in luminal and glandular epithelium with strong staining on Day 19 conceptus. At Day 19 of gestation, expression of EMMPRIN mRNA on luminal epithelium was decreased than that observed at middle of estrous cycle, however, on Day 30 of gestation, slightly increased expression was found at the site of placentation. Expression of matrix metalloproteinase-2 (MMP-2) and MMP-14 mRNA were mainly detected in stroma and their expression also decreased at Day 19 of gestation however it was also expressed at the site of placentation at Day 30 of gestation as observed for EMMPRIN. Expression of MMP-1 or -9 mRNA was very low and was below the detection limit in the cyclic and pregnant endometrium.Conclusion: EMMPRIN from the luminal epithelium may regulate the expression of stromal MMP-2 and -14 suggesting its crucial role in adhesion and fusion of embryo to luminal epithelium by directly itself through physiological tissues remodeling and developmental process, and/or stimulating MMPs to compensate endometrial functions.