Konrad Lutz, Hackethal Andreas, Oehmke Frank, Berkes Eniko, Engel Jörg, Tinneberg Hans-Rudolf
Institute of Gynecology and Obstetrics, Medical Faculty, Justus-Liebig-University, Giessen, Germany
Team Gynecologic Endoscopy, Private Clinic, Hamburg, Germany.
Reprod Sci. 2016 Oct;23(10):1371-80. doi: 10.1177/1933719116641756. Epub 2016 Apr 12.
Clusterin (CLU) is expressed in tissues and body fluids and is altered in some pathologies. In endometriosis, a noninvasive test is still lacking, thus, we analyzed CLU in mucus samples of patients. Additionally, we investigated localization of CLU and the putative CLU receptors (apolipoprotein E receptor 2 [ApoER2], megalin, very low-density lipoprotein receptor [VLDLR], and transforming growth factor β receptor type I and II [TβR1/TβR2]). In mucus samples, CLU levels are modestly, but not significantly, higher in cases with endometriosis compared to cases without endometriosis, however, CLU levels are significantly (P = .02) reduced in patients with endometriosis receiving contraception compared to cases with endometriosis without contraception. Analysis of CLU and CLU receptors showed CLU mainly in the uterine epithelial cells in the majority of glands, but also in endothelial cells. Similarly, ApoER2 and TβR1 could also be found preferentially in the endometrial glands. Whereas ApoER2 staining was strong in the vessels, TβR1 was modestly expressed in vessels and muscle cells. In contrast, staining of VLDLR and TβR2 was modest in the glands but stronger in vessels and muscle cells. Megalin staining was faint in the glands. A similar pattern for these proteins could be observed in adenomyosis. We demonstrate for the first time high concentrations of CLU in mucus samples and significantly reduced CLU levels in cases with endometriosis receiving contraception compared to cases with endometriosis without contraception. Furthermore, we identified uterine epithelial and endothelial cells as the main source of CLU and found different preferential CLU receptor complexes on glands, vessels, and smooth muscle cells.
簇集素(CLU)在组织和体液中表达,且在某些病理状态下会发生改变。在子宫内膜异位症中,目前仍缺乏一种非侵入性检测方法,因此,我们分析了患者黏液样本中的CLU。此外,我们还研究了CLU及其假定受体(载脂蛋白E受体2 [ApoER2]、巨膜蛋白、极低密度脂蛋白受体[VLDLR]以及转化生长因子βⅠ型和Ⅱ型受体[TβR1/TβR2])的定位。在黏液样本中,与无子宫内膜异位症的病例相比,子宫内膜异位症病例的CLU水平略有升高,但无显著差异;然而,与未采取避孕措施的子宫内膜异位症病例相比,采取避孕措施的子宫内膜异位症患者的CLU水平显著降低(P = 0.02)。对CLU及其受体的分析表明,在大多数腺体的子宫上皮细胞中以及内皮细胞中均有CLU表达。同样,ApoER2和TβR1也优先在子宫内膜腺体中被发现。ApoER2在血管中染色较强,而TβR1在血管和肌肉细胞中表达较弱。相比之下,VLDLR和TβR2在腺体中染色较弱,但在血管和肌肉细胞中染色较强。巨膜蛋白在腺体中的染色较淡。在子宫腺肌病中也观察到了这些蛋白的类似表达模式。我们首次证明黏液样本中存在高浓度的CLU,且与未采取避孕措施的子宫内膜异位症病例相比,采取避孕措施的子宫内膜异位症病例的CLU水平显著降低。此外,我们确定子宫上皮细胞和内皮细胞是CLU的主要来源,并在腺体、血管和平滑肌细胞上发现了不同的优先CLU受体复合物。