Wang Haijiao, Kira Yukimi, Hamuro Akihiro, Takase Aki, Tachibana Daisuke, Koyama Masayasu
Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
Department of Research Support Platform, Osaka City University Graduate School of Medicine, Osaka, Japan.
Int Urogynecol J. 2019 Mar;30(3):439-446. doi: 10.1007/s00192-018-3637-z. Epub 2018 Mar 29.
Pelvic organ prolapse (POP) is a multifactorial disorder that impairs the quality of life (QoL) of older women in particular. The purpose of this study was to elucidate the pathogenesis of POP by focusing on the extracellular matrix (ECM).
Patients were classified into two groups-with or without cervical elongation-using the POP quantification system. Specimens were obtained from 29 women with POP during hysterectomy. The expression of fibulin-5, elastin, integrin β1 (ITGβ1), lysyl oxidase-like protein-1 (LOXL1) and collagen in the vagina, uterosacral ligament, and uterine cervix was investigated by quantitative real-time polymerase chain reaction (RT-PCR) and correlation between gene levels and severity of POP examined. The location of proteins was analyzed using immunohistochemical staining and expression of fibulin-5 protein analyzed by Western blotting.
Fibulin-5 and elastin were mainly expressed in lamina propria and fibromuscular layers of the vagina and uterosacral ligament. Gene levels of fibulin-5 and ITGβ1 in uterosacral ligaments increased with severity of POP in women with cervical elongation, while no correlation was observed in women with a normal cervix. In women with uterine cervical elongation, each ECM-related gene significantly increased with POP staging. Furthermore, fibulin-5 protein also increased in the uterosacral ligament and uterine cervix.
The severity of POP and gene expression of ECM-related proteins were inversely correlated in vaginal tissue in a normal and elongated cervix. These results suggested that the differing progression of the two types of POP have a relationship with ECM-related protein.
盆腔器官脱垂（POP）是一种多因素疾病，尤其会损害老年女性的生活质量（QoL）。本研究旨在通过关注细胞外基质（ECM）来阐明POP的发病机制。
使用POP量化系统将患者分为两组——有或无宫颈延长。在子宫切除术中从29例患有POP的女性身上获取标本。通过定量实时聚合酶链反应（RT-PCR）研究阴道、子宫骶韧带和子宫颈中纤连蛋白-5、弹性蛋白、整合素β1（ITGβ1）、赖氨酰氧化酶样蛋白-1（LOXL1）和胶原蛋白的表达，并检测基因水平与POP严重程度之间的相关性。使用免疫组织化学染色分析蛋白质的定位，并通过蛋白质印迹法分析纤连蛋白-5蛋白的表达。
纤连蛋白-5和弹性蛋白主要表达于阴道和子宫骶韧带的固有层和纤维肌层。宫颈延长的女性中，子宫骶韧带中纤连蛋白-5和ITGβ1的基因水平随POP严重程度增加，而宫颈正常的女性中未观察到相关性。在宫颈延长的女性中，每个与ECM相关的基因随POP分期显著增加。此外，子宫骶韧带和子宫颈中的纤连蛋白-5蛋白也增加。
在正常和延长宫颈的阴道组织中，POP的严重程度与ECM相关蛋白的基因表达呈负相关。这些结果表明，两种类型POP不同的进展与ECM相关蛋白有关。
