Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis
Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis
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DOI：
10.1093/humrep/deu146
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发表时间：
2014-08-01
影响因子：
6.1
通讯作者：
Carson, D. D.
中科院分区：
文献类型：
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作者：
Dharmaraj, N.;Chapela, P. J.;Carson, D. D.
跨膜粘蛋白MUC1、MUC4和MUC16在子宫内膜异位症中的表达与正常子宫内膜相比有差异吗？研究发现，跨膜粘蛋白在月经周期中在正常子宫内膜中的表达没有显著变化，在子宫内膜异位症中相对于上皮标志物细胞角蛋白-18(KRT18)也没有改变。在包括子宫内膜异位症在内的几种病理情况下，血清中正常情况下占据简单上皮顶面的跨膜粘蛋白片段MUC1、MUC4和MUC16水平升高。针对12例子宫内膜异位症患者和31例非子宫内膜异位症患者的粘蛋白表达改变可能促进不孕症或子宫内膜病变的实验室研究。从子宫内膜异位症患者的异位和在位内膜活检组织中提取总RNA。定量(Q)-RT-PCR分析粘蛋白MUC1、MUC4和MUC16与上皮标志物细胞角蛋白-18(KRT18)或β-肌动蛋白(ACTB)的关系。对增生期和分泌期中期子宫内膜活检组织冰冻切片进行MUC1、MUC4和MUC16免疫组织化学染色。qRT-PCR分析表明，这些粘蛋白在月经周期中没有显著变化，在子宫内膜异位症患者中也没有相对于上皮标志物KRT18的改变。在所有条件下，相对于MUC1和MUC16，MUC4mRNA的表达水平非常低。异位内膜和在位内膜组织中MUC1和MUC16的表达差异无统计学意义。异位内膜组织中MUC4的表达也未见明显升高。3种粘蛋白的免疫组织化学染色显示，MUC1和MUC16在子宫内膜上皮尖表面均有较强的表达，而MUC4几乎不表达，qRT-PCR是检测粘蛋白的主要方法。对III-IV期子宫内膜异位症组织的进一步研究将有助于确定在子宫内膜异位症的后期阶段是否会发生MUC1和MUC16表达的变化，或者MUC4表达是否增加。我们报告了主要跨膜粘蛋白MUC1、MUC4和MUC16在正常周期子宫内膜和子宫内膜异位症中相对于上皮标志物KRT18的全面比较概况，并指出其结构性表达。以前的研究已经描述了单个粘蛋白相对于β-肌动蛋白的表达，并表明在黄体期积累。因此，这些不同的解释似乎反映了黄体期子宫内膜上皮含量的增加。这项研究得到了以下支持：NIH R01HD29963到D.D.C.；NIH U54HD007495到S.M.H.；NIH R01HD067721到S.L.Y.和B.A.L.。作者没有相互竞争的利益需要声明。
Are the transmembrane mucins, MUC1, MUC4 and MUC16, differentially expressed in endometriosis compared with normal endometrium?This study revealed that transmembrane mucin expression does not vary significantly in normal endometrium during the menstrual cycle and is not altered in endometriosis relative to the epithelial marker, cytokeratin-18 (KRT18).Increased serum levels of the transmembrane mucin fragments MUC1, MUC4 and MUC16 that normally dominate the apical surface of simple epithelia are found in several pathological conditions, including endometriosis. Altered mucin expression in gynecologic diseases may promote infertility or endometrial pathologies.This was a laboratory-based study of samples from 12 endometriosis patients as well as non-endometriosis control samples obtained from 31 patients.Total RNA was isolated from endometrial biopsies of ectopic and eutopic endometrium from women with endometriosis and control patients from different stages of the menstrual cycle. Quantitative (q)-RT-PCR analyses were performed for the mucins, MUC1, MUC4 and MUC16, relative to the epithelial marker, cytokeratin-18 (KRT18), or beta-actin (ACTB). Frozen sections from endometrial biopsies of proliferative and mid-secretory stage women with endometriosis were immunostained for MUC1, MUC4 and MUC16.qRT-PCR analyses of MUC1 and MUC16 mRNA revealed that these mucins do not vary significantly during the menstrual cycle nor are they altered in women with endometriosis relative to the epithelial marker, KRT18. MUC4 mRNA is expressed at very low levels relative to MUC1 and MUC16 under all conditions. There was little difference in MUC1 and MUC16 expression between eutopic endometrial and ectopic endometriotic tissues. MUC4 expression also was not significantly higher in the ectopic endometriotic tissues. Immunostaining for all three mucins reveals robust expression of MUC1 and MUC16 at the apical surfaces of endometrial epithelia, but little to no staining for MUC4.qRT-PCR analysis was the main method used for mucin detection. Additional studies with stage III-IV endometriotic tissue would be useful to determine if changes in MUC1 and MUC16 expression occur, or if MUC4 expression increases, at later stages of endometriosis.We report a comprehensive comparative profile of the major transmembrane mucins, MUC1, MUC4 and MUC16, relative to the epithelial marker, KRT18, in normal cycling endometrium and in endometriosis, and indicate constitutive expression. Previous studies have profiled the expression of individual mucins relative to beta-actin and indicate accumulation in the luteal phase. Thus, these differences in interpretation appear to reflect the increased epithelial content of endometrium during the luteal phase.This study was supported by: NIH R01HD29963 to D.D.C.; NIH U54HD007495 to S.M.H.; and NIH R01HD067721 to S.L.Y. and B.A.L. The authors have no competing interests to declare.