Differential gene expression of extracellular-matrix-related proteins in the vaginal apical compartment of women with pelvic organ prolapse
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Introduction and hypothesis
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.
KeywordsPelvic organ prolapse Cervical elongation Fibulin-5 Integrin β1 Lysyl oxidase-like protein-1 Extracellular matrix
This work was supported, in part, by Grants-in-Aid for Scientific Research (No.16 K11147) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. The authors would like to acknowledge the doctors in the Department of Obstetrics and Gynecology for their assistance with sample collection, Dr. Ji-Young Hong (BioLead Inc., Korea), Keisuke Inoue and Yoriko Yabunaka (Research support platform of Osaka City University Graduate School of Medicine) for special technical assistance.
Compliance with ethical standards
Conflicts of interest
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