Maoga Jane B, Riaz Muhammad A, Mwaura Agnes N, Mecha Ezekiel, Omwandho Charles O A, Scheiner-Bobis Georgios, Meinhold-Heerlein Ivo, Konrad Lutz
Center of Gynecology and Obstetrics, Faculty of Medicine, Justus Liebig University Giessen, 35392 Giessen, Germany.
Department of Biochemistry, University of Nairobi, Nairobi P.O. Box 30197-00100, Kenya.
Biomedicines. 2023 Oct 9;11(10):2730. doi: 10.3390/biomedicines11102730.
Membrane type-matrix metalloproteinases (MT-MMPs) are a subgroup of the matrix metalloproteinases (MMPs) family and are key molecules in the degradation of the extracellular matrix. Membrane type-1 matrix metalloproteinase (MT1-MMP, MMP14) is often deregulated in different cancer tissues and body fluids of human cancer patients; however, MT1-MMP levels in endometriosis and adenomyosis patients are currently unknown.
Tissue samples from patients with and without endometriosis or adenomyosis were analyzed with immunohistochemistry for the localization of MT1-MMP. Serum and endocervical mucus samples from patients with and without endometriosis or adenomyosis were investigated with MT1-MMP ELISAs.
MT1-MMP was localized preferentially in the glands of eutopic and ectopic endometrium. MT1-MMP protein levels are significantly reduced in ovarian endometriosis (HSCORE = 31) versus eutopic endometrium (HSCORE = 91) and adenomyosis (HSCORE = 149), but significantly increased in adenomyosis (HSCORE = 149) compared to eutopic endometrium (HSCORE = 91). Similarly, analysis of the levels of MT1-MMP using enzyme-linked immune assays (ELISAs) demonstrated a significant increase in the concentrations of MT1-MMP in the serum of endometriosis patients (1.3 ± 0.8) versus controls (0.7 ± 0.2), but not in the endocervical mucus. Furthermore, MT1-MMP levels in the endocervical mucus of patients with endometriosis were notably reduced in patients using contraception (3.2 ± 0.4) versus those without contraception (3.8 ± 0.2).
Taken together, our findings showed an opposite regulation of MT1-MMP in the tissue of ovarian endometriosis and adenomyosis compared to eutopic endometrium without endometriosis but increased serum levels in patients with endometriosis.
膜型基质金属蛋白酶(MT - MMPs)是基质金属蛋白酶(MMPs)家族的一个亚群,是细胞外基质降解的关键分子。膜型 - 1基质金属蛋白酶(MT1 - MMP,MMP14)在人类癌症患者的不同癌组织和体液中常出现失调;然而,目前子宫内膜异位症和子宫腺肌病患者的MT1 - MMP水平尚不清楚。
采用免疫组织化学方法分析有或无子宫内膜异位症或子宫腺肌病患者的组织样本中MT1 - MMP的定位。采用MT1 - MMP酶联免疫吸附测定(ELISA)法检测有或无子宫内膜异位症或子宫腺肌病患者的血清和宫颈黏液样本。
MT1 - MMP主要定位于在位和异位子宫内膜的腺体中。与在位子宫内膜(组织学评分=91)和子宫腺肌病(组织学评分=149)相比,卵巢子宫内膜异位症(组织学评分=31)中MT1 - MMP蛋白水平显著降低,但与在位子宫内膜(组织学评分=91)相比,子宫腺肌病(组织学评分=149)中MT1 - MMP蛋白水平显著升高。同样,使用酶联免疫测定(ELISA)法分析MT1 - MMP水平显示,子宫内膜异位症患者血清中MT1 - MMP浓度(1.3±0.8)显著高于对照组(0.7±0.2),但宫颈黏液中无此差异。此外,使用避孕药的子宫内膜异位症患者宫颈黏液中的MT1 - MMP水平(3.2±0.4)明显低于未使用避孕药的患者(3.8±0.2)。
综上所述,我们的研究结果表明,与无子宫内膜异位症的在位子宫内膜相比,卵巢子宫内膜异位症和子宫腺肌病组织中MT1 - MMP的调节情况相反,但子宫内膜异位症患者血清水平升高。