The amount and activity of active matrix metalloproteinase 13 is suppressed by estradiol and progesterone in human pelvic floor fibroblasts.
The amount and activity of active matrix metalloproteinase 13 is suppressed by estradiol and progesterone in human pelvic floor fibroblasts.
复制标题
人盆底成纤维细胞中活性基质金属蛋白酶 13 的量和活性受到雌二醇和孕酮的抑制。
DOI：
10.1095/biolreprod.108.072462
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发表时间：
2009
影响因子：
3.6
通讯作者：
Moalli,PamelaA
中科院分区：
文献类型：
--
作者：
Zong,Wenjun;Meyn,LeslieA;Moalli,PamelaA
基质金属蛋白酶13（MMP 13）作为纤维状胶原的关键降解物，可能参与盆腔器官脱垂的进展。在这里，我们的目的是确定调节MMP 13的雌二醇和孕酮在阴道支持组织。用17-β-雌二醇（E2）、孕酮（P4）、E2 + P4或E2 + ICI 182，780（ICI）处理从3名绝经前和3名绝经后脱垂妇女的骨盆腱筋膜弓培养的成纤维细胞。胶原酶抑制剂I（CI）和MG-132被用来研究MMP 13降解成非活性片段（断裂）的机制。通过比较卵巢切除（ovx）与假手术大鼠的组织来评估MMP 13在体内的调节。MMP 13的表达（酶原和活性和片段形式）通过Western免疫印迹定量，MMP 13酶活性使用底物降解测定法测定。在激素的存在下，细胞活性MMP 13和MMP 13蛋白水解活性的量降低。这种减少被增加的酶原和片段形式所抵消。MG-132而不是CI抑制细胞MMP 13片段化。活性MMP 13在大鼠OVX后增加，并被E2 + P4补充抑制。活性MMP 13在体内和体外被雌二醇和孕酮抑制，表明对阴道支持组织退化的保护作用。
As a key degrader of fibrillar collagens, matrix metalloproteinase 13 (MMP13), may contribute to the progression of pelvic organ prolapse. Here we aimed to define the regulation of MMP13 by estradiol and progesterone in the vaginal supportive tissues. Fibroblasts cultured from the arcus tendineous fasciae pelvis of three pre- and three postmenopausal women with prolapse were treated with 17-beta-estradiol (E2), progesterone (P4), E2 + P4, or E2 + ICI 182,780 (ICI). Collagenase inhibitor I (CI) and MG-132 were employed to investigate the mechanism of MMP13 degradation into inactive fragments (fragmentation) by hormones. The regulation of MMP13 in vivo was assessed by comparing tissues of ovariectomized (ovx) vs. sham-operated rats. Expression of MMP13 (proenzyme and active and fragment forms) was quantitated by Western immunoblotting, and MMP13 enzymatic activity was measured using a substrate degradation assay. The amount of cellular active MMP13 and MMP13 proteolytic activity decreased in the presence of hormones. The decrease was paralleled by increased proenzyme and fragment forms. MG-132, not CI, suppressed cellular MMP13 fragmentation. Active MMP13 increased in rats following ovx and was suppressed by E2 + P4 supplementation. Active MMP13 is suppressed in vivo and in vitro by estradiol and progesterone, suggesting a protective effect against vaginal supportive tissue deterioration.