Transcriptional Regulation of Connective Tissue Metabolism Genes in Women With Pelvic Organ Prolapse.
Transcriptional Regulation of Connective Tissue Metabolism Genes in Women With Pelvic Organ Prolapse.
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DOI：
10.1097/spv.0000000000000337
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发表时间：
2017
影响因子：
1.6
通讯作者：
Damaser MS
中科院分区：
文献类型：
--
作者：
Borazjani A;Kow N;Harris S;Ridgeway B;Damaser MS
为了比较患有和不患有盆腔器官脱垂 (POP) 的女性中参与细胞外基质代谢和组织细胞构成的关键基因之间的表达和关系的差异，从 30 名女性中获得了总共 80 个活检组织（前袖套、后袖套和/或前缘）：n = 10 例绝经前无 POP（对照），n = 10 例绝经前 POP，n = 10 例。 绝经后患有 POP。使用定量逆转录酶聚合酶链反应评估 BMP1、COL1、COL3、RXFP1、MMP2、TIMP2 和 TIMP3 的基因表达。 H&E 染色用于评估结缔组织层的细胞结构。酌情使用 Kruskal-Wallis、Mann-Whitney、Pearson 相关或线性回归分析。与对照组相比，POP 患者的 BMP1 表达显着上调。所有组中 BMP1 表达与 COL1 表达相关，但仅与对照组中 TIMP3 表达相关。同样，在 POP 女性中，COL3 表达与 RXFP1 表达相关，但在对照组中则不然。与其他组相比，患有 POP 的绝经前女性中 COL1 和 COL3 表达之间的依赖性程度（回归线的斜率）显着升高。与患有 POP 的绝经前女性相比，绝经后女性中 COL1-COL3、COL3-MMP2、COL1-RXFP1 和 COL3-RXFP1 表达之间的斜率显着较低。总体组织细胞结构没有发现差异。 BMP1 表达可能在 POP 的病理生理学中发挥重要作用。所有组中 BMP1 表达与 COL1 表达相关的发现表明 BMP1 与阴道壁胶原合成之间存在保守关联。 COL1-COL3 表达之间的斜率升高可能与 POP 的早期（绝经前）发展有关。 RXFP1 在绝经后妇女中的表达及其改变的基因间调节表明 RXFP1 在妊娠期外结缔组织代谢中的作用。
To compare differences in expressions and relationships between key genes involved in extracellular matrix metabolism and tissue cellularity in women with and without pelvic organ prolapse (POP) A total of 80 biopsies (anterior cuff, posterior cuff, and/or leading edge) were obtained from 30 women: n=10 premenopausal without POP (controls), n=10 premenopausal with POP, and n=10 postmenopausal with POP. Quantitative reverse-transcriptase polymerase chain reaction was used to assess gene expression of BMP1, COL1, COL3, RXFP1, MMP2, TIMP2, and TIMP3. H&E staining was used to assess cellularity of the connective tissue layer. Kruskal-Wallis, Mann-Whitney, Pearson’s correlation, or linear regression analyses were used as appropriate. BMP1 expression was significantly upregulated in patients with POP compared to controls. BMP1 expression was correlated with COL1 expression in all groups, but only correlated with TIMP3 expression in controls. Similarly, COL3 expression was correlated with RXFP1 expression in women with POP but not in controls. The degree of dependence (slope of the regression line) between COL1 and COL3 expression was significantly elevated in premenopausal women with POP compared to both other groups. The slopes between COL1-COL3, COL3-MMP2, COL1-RXFP1, and COL3-RXFP1 expression were significantly lower in postmenopausal women compared to premenopausal women with POP. No differences were found in overall tissue cellularity. BMP1 expression may play a significant role in the pathophysiology of POP. The finding that BMP1 expression was correlated with COL1 expression in all groups suggests a conserved association between BMP1 and collagen synthesis in the vaginal wall. The elevated slope between COL1-COL3 expressions may be associated with early (premenopausal) development of POP. The expression of RXFP1 in postmenopausal women and its altered inter-gene regulation, suggests a role for RXFP1 in connective tissue metabolism outside of pregnancy.