Expression of membrane-type 5 matrix metalloproteinase in human endometrium and endometriosis
Expression of membrane-type 5 matrix metalloproteinase in human endometrium and endometriosis
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DOI：
10.1080/09513590701556921
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发表时间：
2007-10-01
影响因子：
2
通讯作者：
Kaufmann, Manfred
中科院分区：
文献类型：
--
作者：
Gaetje, Regine;Holtrich, Uwe;Kaufmann, Manfred
背景金属蛋白酶（MMPs）是一个蛋白水解酶家族，参与组织重塑和细胞迁移。子宫内膜组织重塑在月经周期中进行，需要几种不同MMP的临时和空间平衡表达。MMPs的各种成员似乎也在子宫内膜异位症的侵袭过程中发挥重要作用;然而，到目前为止，只有有限数量的研究集中在膜相关MMPs上。本研究应用微阵列杂交、实时荧光定量PCR和免疫荧光技术检测了膜型5型金属蛋白酶（MT5-MMP）在人子宫内膜和子宫内膜异位症病变中的表达。基因芯片表达分析以及PCR均显示MT5-MMP在正常人子宫内膜中表达，并且在所分析的大多数腹膜子宫内膜异位症病变中转录水平强烈升高。此外，我们检测到MT5-MMP在子宫内膜异位症患者的在位子宫内膜中的表达增强，进一步支持MT5-MMP在子宫内膜异位症形成中的作用。采用免疫组化方法检测MT5-MMP的细胞内定位和组织分布。虽然MT5-MMP抗原的表达可以清楚地归因于上皮细胞的膜，但在子宫内膜组织的各个隔室中观察到MT5-MMP的高度复杂的差异免疫组织化学染色。MT5-MMP在子宫内膜上皮细胞中表达最强，而在子宫内膜腺体中则多为部分表达。我们的微阵列分析和MT5-MMP转录的实时PCR可能指向子宫内膜异位症患者的子宫内膜中升高的组织重塑和细胞迁移，正如相关MMPs的功能所暗示的。
Background. The metalloproteinases (MMPs) are a family of proteolytic enzymes involved in tissue remodeling and cell migration. Endometrial tissue remodeling proceeds during the menstrual cycle and requires a temporary and spatially balanced expression of several different MMPs. Various members of the MMPs also seem to play an important role in the invasion process of endometriosis; however, so far only a limited number of studies have focused on membrane-associated MmPs.Methods. The present study investigated the expression of membrane-type 5 metalloproteinase (MT5-MMP) in the human endometrium and endometriotic lesions by microarray hybridization, real-time polymerase chain reaction (PCR) and immunofluorescence.Results. Both the gene chip expression analyses as well as PCR indicated expression of MT5-MMP in normal human endometrium and strongly elevated transcript levels in most peritoneal endometriosis lesions analyzed. Moreover we detected enhanced MT5-MMP expression in the eutopic endometrium from patients suffering from endometriosis, further supporting a role of MT5-MMP in the formation of endometriosis. Immunohistochemical analysis was used to determine the intracellular localization and tissue distribution of MT5-MMP. While the MT5-MMP antigen expression could be clearly attributed to the membrane of epithelial cells, a highly complex differential immunohistochemical staining of MT5-MMP in the various compartments of endometrial tissue was observed. The strongest staining was seen in luminal epithelial cells, whereas endometrial glands frequently showed partial expression of MT5-MMP.Conclusion. Our microarray analysis and real-time PCR of MT5-MMP transcripts may point to an elevated tissue remodeling and cell migration in endometrium from endometriosis patients as implied by the function of related MMPs.