Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China.
Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
Int Urogynecol J. 2021 Aug;32(8):2273-2281. doi: 10.1007/s00192-020-04446-7. Epub 2020 Jul 31.
This study aimed to compare the expression levels of extracellular matrix (ECM) and apoptosis proteins in the uterosacral ligament (USL) of patients with and without pelvic organ prolapse (POP).
The USL were obtained from patients with POP-Q ≥ III (n = 35) and without POP (n = 20). Immunohistochemistry (IHC) staining and RT-qPCR were conducted to assess the protein and mRNA levels, respectively. The levels of type I collagen (COLI), type III collagen (COLIII), matrix metalloproteinase (MMP)1, MMP2, MMP9, tissue inhibitor of metalloproteinase (TIMP)1, TIMP2, estrogen receptor (ER)α, ERβ and apoptosis-related gene B cell lymphoma 2 (Bcl-2)-associated agonist of cell death (Bad) and Bcl-2-associated X (Bax) in the USL were analyzed.
The protein expression and mRNA levels of MMP2 and MMP9, mRNA levels of BAD and BAX, and protein expression of active cleaved-Caspase3 were significantly higher in the POP group. There were no evident differences in COLIII, MMP1 or ERβ expression at either the mRNA or protein level or in TIMP1, TIMP2 or Caspase3 by IHC between the two groups. However, obvious decreases in COLI and ERα were evident at both the mRNA and protein levels in the POP group, and the mRNA levels of TIMP1 and TIMP2 were also decreased compared to those of the control group.
ECM in the USL tissues of POP patients is remodeled compared with non-POP patients and is characterized by decreased synthesis and increased degradation of collagen; moreover, the levels of the main proteins involved in apoptosis are increased in POP tissue.
本研究旨在比较有和没有盆腔器官脱垂(POP)的患者的子宫骶韧带(USL)中细胞外基质(ECM)和凋亡蛋白的表达水平。
从 POP-Q≥III 的患者(n=35)和没有 POP 的患者(n=20)中获得 USL。通过免疫组化(IHC)染色和 RT-qPCR 分别评估蛋白和 mRNA 水平。分析 USL 中 I 型胶原(COLI)、III 型胶原(COLIII)、基质金属蛋白酶(MMP)1、MMP2、MMP9、金属蛋白酶组织抑制剂(TIMP)1、TIMP2、雌激素受体(ER)α、ERβ 和凋亡相关基因 B 细胞淋巴瘤 2(Bcl-2)相关的细胞死亡激动剂(Bad)和 Bcl-2 相关 X(Bax)的蛋白表达和 mRNA 水平。
POP 组的 MMP2 和 MMP9 的蛋白表达和 mRNA 水平、BAD 和 BAX 的 mRNA 水平以及活性切割 Caspase3 的蛋白表达显著升高。在 mRNA 或蛋白水平上,COLIII、MMP1 或 ERβ 表达或在 IHC 上的 TIMP1、TIMP2 或 Caspase3 之间在两组之间没有明显差异。然而,POP 组的 COLI 和 ERα 的 mRNA 和蛋白水平均明显降低,与对照组相比,TIMP1 和 TIMP2 的 mRNA 水平也降低。
与非 POP 患者相比,POP 患者的 USL 组织中的 ECM 被重塑,表现为胶原蛋白合成减少和降解增加;此外,POP 组织中参与凋亡的主要蛋白水平升高。