Expression and significance of lysyl oxidase-like 1 and fibulin-5 in the cardinal ligament tissue of patients with pelvic floor dysfunction

Abstract

Pelvic organ prolapse (POP) is a disabling disorder in women characterized by a loss of pelvic floor support, leading to the herniation of the uterus into or through the vagina. POP is a complex problem that likely involves multiple mechanisms with limited therapies available, and is associated with defects in connective tissue including elastic fibers. This study was designed to investigate the expression of fibulin-5 and lysyl oxidase-like 1 (LOXL1) in the cardinal ligament in samples taken from the POP group compared to the non-POP group. Specimens were obtained during abdominal hysterectomy from the cardinal ligament of 53 women with POP and 25 age- and parity- matched women with non-POP among post-menopausal women with benign gynecologic pathology. Protein expression was evaluated using the immunohistochemical staining method. For statistical analyses, chi-square test and Spearman's correlation were used with the statistical package SPSS13.0 system. Our results showed that both fibulin-5 and LOXL1 expressions were decreased in the cardinal ligament in the POP group compared to the non-POP group (P < 0.05). The expression of fibulin-5 and LOXL1 were correlated closely with the stage of POP, accompanied by stress urinary incontinence and frequency of vaginal delivery (P < 0.05), but had no relationship with post-menopausal state (P > 0.05). The expression of fibulin-5 was positively associated with LOXL1 in POP (P < 0.05). We conclude that changes in fibulin-5 and LOXL1 expression may play a role in the development of POP.

Human copper-dependent amine oxidases

“…In a different study, a role for LOXL1 in elastic fiber renewal in adult tissues was proposed, based on high incidence of pelvic organ prolapse (POP) and permanent damage to the pelvic floor in post partum LOXL1-null mice (110). Subsequent studies of human populations have produced conflicting data regarding the role of LOXL1 in POP: one group has reported an increase in LOXL1 mRNA and protein in the uterosacral ligaments of patients with POP (111), while others report that expression of LOXL1 mRNA (89,112,113) and protein (114,115) are significantly down-regulated in the pelvic connective tissues of POP patients. While the majority of the data support the hypothesis that LOXL1 plays a critical role in elastin maturation, additional investigation is needed to resolve this discrepancy.…”

Transplantation of bone marrow-derived mesenchymal stem cells expressing elastin alleviates pelvic floor dysfunction

“…Elastin helps tissues to stretch and return to their original shape without energy input, which is extremely important in the regenerative system. Many studies have shown that elastin metabolism is affected in PFD because of increased degradation, abnormal synthesis, and interruption in elastin homeostasis [ 17 – 20 ].…”

MicroRNA-29 facilitates transplantation of bone marrow-derived mesenchymal stem cells to alleviate pelvic floor dysfunction by repressing elastin

“…It functions to facilitate the stretch and return of tissues to their original form in the absence of energy. Metabolism of elastin has been shown to be affected in PFD as a result of abnormal synthesis, interruption in homeostasis, as well as increased degradation [19–22]. Weakened connective tissues in the pelvis are thought to contribute to pathophysiological development of PFD.…”