Furthermore, the cytotoxic effect of hydrogen

Uterosacral ligament (USL) were collected to identify the oxidativeĭamage, and assess whether there are differences between women withĪnd without POP. In the present study, this hypothesis was tested The case, it may assist in developing novel clinic therapeutic Thus, the present study hypothesized that OS may contribute toĬollagen metabolic disorder in the pathogenesis of POP. OS is involved in cardiovascular remodeling and fibrotic disordersīy activating MMPs, and reducing collagen synthesis in fibroblasts Messengers modulating specific signaling pathways ( 14). Oxidative damage to cell organisms, including deoxyribonucleic acid Neutralizing ability of the redox system in cells, resulting in OS reflects a status of imbalance, in whichĮxcessive accumulated reactive oxygen species (ROS) exceeds the Proliferation in pelvic connective tissue in women with POPĬonsidered to be the molecular basis facilitating the incidence and Together with upregulated cell apoptosis and downregulated Previous studies have demonstratedĪnd hyperfunction of matrix metalloproteinases (MMPs) ( 11, 12), Aging and vaginal childbirth are wellĮstablished risk factors, and other factors, including obesity,Ĭhronic constipation and declined hormonal status (menopause), haveĪlso been reported to be associated with prolapse ( 6). POP is considered to be a multifactorialĮtiological disease ( 5, 6). However, the etiology and pathophysiological mechanisms remain toīe fully elucidated. Has become one of the most common indications for gynecological Terms of poor life quality and increasing economic burden ( 1– 3), and Problem, which adversely affects 50% of women >50 years old, in Pelvic organ prolapse (POP) is a global health

These results suggested that OS may be involved in the pathophysiology of POP by contributing to collagen metabolic disorder in a severity‑dependent manner in hUSLFs, possibly through the regulation of MMPs, TIMPs and TGF‑β1 indirectly. The expression levels of MMP‑2, TIMP‑2 and TGF‑β1 exhibited corresponding changes with the OS levels. Collagen metabolism was regulated by H2O2 exposure in a concentration‑dependent manner, in which lower concentrations of H2O2 (0.1‑0.2 mM) stimulated the anabolism of COL1A1, whereas a higher concentration (0.4 mM) promoted catabolism. The results showed that the expression levels of 8‑OHdG and 4‑HNE in the POP group were significantly higher, compared with those in the control group. The primary cultured hUSLFs were treated with exogenous H2O2 to establish an original OS cell model, in which the expression levels of collagen, type 1, α1 (COL1A1), matrix metalloproteinase (MMP)‑2, tissue inhibitor of metalloproteinase (TIMP)‑2 and transforming growth factor (TGF)‑β1 were evaluated by western blot and reverse transcription‑quantitative polymerase chain reaction analyses. In the present study, 8‑hydroxyguanosine (8‑OHdG) and 4 hydroxynonenal (4‑HNE), as oxidative biomarkers, were examined by immunohistochemistry to evaluate oxidative injury in USL sections in POP (n=20) and non‑POP (n=20) groups. The present study aimed to clarify whether OS exists in the uterosacral ligament (USL) with POP, and to investigate the precise role of OS in collagen metabolism in human USL fibroblasts (hUSLFs). Oxidative stress (OS) is a well‑recognized mechanism involved in fiber metabolic disorders. The loss of extracellular matrix protein has been considered to be the most important molecular basis facilitating the development of POP. Pelvic organ prolapse (POP) is a global health problem, for which the pathophysiological mechanism remains to be fully elucidated.

Collagen catabolism