Elastin metabolism in pelvic tissues: Is it modulated by reproductive hormones?
Elastin metabolism in pelvic tissues: Is it modulated by reproductive hormones?
复制标题
DOI：
10.1016/j.ajog.2004.11.027
复制
发表时间：
2005-05-01
影响因子：
9.8
通讯作者：
Polan, ML
中科院分区：
文献类型：
--
作者：
Chen, B;Wen, Y;Polan, ML
目的：本研究的目的是研究松弛素对盆腔成纤维细胞细胞外基质蛋白表达的影响，所述成纤维细胞培养自压力性尿失禁女性与无症状对照受试者相比。绝经前压力性尿失禁妇女和正常妇女尿道周围阴道壁成纤维细胞的研究（在月经周期的增殖期和分泌期）用增加浓度的松弛素（0-500 ng/mL）刺激。通过酶谱法对上清液取样用于基质金属蛋白酶-2和基质金属蛋白酶-9。用Western blot法检测金属蛋白酶组织抑制剂-1和-2和α-1抗胰蛋白酶。总弹性蛋白酶活性通过琥珀酰化弹性蛋白产生游离氨基来测量。增加浓度的α-1抗胰蛋白酶被添加到细胞裂解液中，以评估总弹性蛋白酶活性inhibit 1 n.Results. Recessive阶段压力性尿失禁成纤维细胞表现出增加基质金属蛋白酶-2和没有变化的基质金属蛋白酶-9和组织抑制剂的金属蛋白酶-1和-2的表达与松弛素浓度增加。对照组的细胞显示基质金属蛋白酶-2和-9的表达增加，但金属蛋白酶组织抑制剂没有变化。松弛素刺激下，分泌期压力性尿失禁成纤维细胞对基质金属蛋白酶或金属蛋白酶组织抑制剂的表达无反应。分泌期对照成纤维细胞通过增加基质金属蛋白酶-2和-9以及金属蛋白酶组织抑制剂-2来反应。关于总弹性蛋白酶活性和α-1抗胰蛋白酶表达，增加松弛素剂量似乎通过降低增殖期细胞中α-1抗胰蛋白酶的表达或增加分泌期细胞中总弹性蛋白酶活性来增加压力性尿失禁细胞中的弹性蛋白溶解活性。成纤维细胞总弹性蛋白酶活性被抑制，通过增加浓度的α-1 antitrypsin.Conclusion：弹性蛋白酶活性似乎增加松弛素刺激的压力性尿失禁成纤维细胞通过降低抑制剂α-1 antitrypsin生产或增加弹性蛋白酶活性。(c)2005年爱思唯尔公司All rights reserved.
Objective: The purpose of this study was to investigate the effect of relaxin on extracellular matrix protein expression in pelvic fibroblasts that were cultured from women with stress urinary incontinence compared with asymptomatic control subjects.Study design: Periurethral vaginal wall fibroblasts from premenopausal women with stress urinary incontinence and continent women (in both the proliferative and secretory phase of the menstrual cycle) were stimulated with increasing concentrations of relaxin (0-500 ng/mL). The supernatant was sampled for matrix metalloproteinase-2 and -9 by zymography. Tissue inhibitors of metalloproteinase-1 and -2 and alpha-1 antitrypsin were evaluated with Western blot. Total elastase activity was measured by generation of free amino groups from succinylated elastin. Increasing concentrations of alpha-1 antitrypsin were added to cell lysate to evaluate total elastase activity inhibition.Results: Proliferative-phase stress urinary incontinence fibroblasts demonstrated an increase in matrix metalloproteinase-2 and no change in matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 and -2 expressions with increasing relaxin concentrations. Cells from control subjects showed increased expression of matrix metalloproteinase-2 and -9, but no change in tissue inhibitors of metalloproteinases. Secretory-phase stress urinary incontinence fibroblasts showed no response in matrix metalloproteinase or tissue inhibitors of metalloproteinase expressions with relaxin stimulation. Secretory-phase control fibroblasts reacted by increasing matrix metalloproteinase-2 and -9 and tissue inhibitors of metalloproteinase-2. With respect to total elastase activity and alpha-1 antitrypsin expression, increasing doses of relaxin appear to increase elastolytic activity in stress urinary incontinence cells by decreasing the expression of alpha-1 antitrypsin in proliferative phase cells or increasing the total elastase activity in secretory phase cells. Fibroblast total elastase activity was inhibited by increasing concentrations of alpha-1 antitrypsin.Conclusion: Elastase activity appears to be increased in relaxin-stimulated stress urinary incontinence fibroblasts by either decreased inhibitor alpha-1 antitrypsin production or increased elastase activity. (c) 2005 Elsevier Inc. All rights reserved.