Cellular senescence: A pathogenic mechanism of pelvic organ prolapse (Review)

Huang, Liwei; Zhao, Zhiwei; Wen, Jiqiu; Wang, Ling; Miao, Yong; Wu, Jiang

doi:10.3892/mmr.2020.11339

Cited by 25 publications

(22 citation statements)

References 81 publications

(105 reference statements)

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“…After acute or subacute injury, oxidative stress will occur in response to adverse stimuli. 20 Nuclear factor-erythroid 2-related factor 2 is a basic leucine zipper that is the major regulatory transcription factor of cellular antioxidant defense system. 21 It can coordinate various responses in response to various forms of Nrf2 on Phenotype Changes of Macrophages ORIGINAL RESEARCH n stress and inflammatory process and maintain the stability of the intracellular environment.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Nrf2 on Phenotype Changes of Macrophages in the Anterior Vaginal Wall of Women With Pelvic Organ Prolapse

Liu

Chen

et al. 2022

Female Pelvic Med Reconstr Surg

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ObjectiveThe aim of this study was to observe the effect of nuclear factor-erythroid 2-related factor 2 (Nrf2) on the phenotype changes of macrophages in the anterior vaginal wall of patients with pelvic organ prolapse (POP).MethodsThe tissues of the anterior vaginal wall of the control group (n = 30) and POP groups (n = 60) were collected during operation. The expressions of Nrf2, iNOS (representative factor of M1 macrophages), and CD206 (representative factor of M2 macrophages) were determined by immunohistochemical staining and Western blot. Morphological changes and collagen distribution of the anterior vaginal wall were observed by hematoxylin-eosin staining and Masson trichrome staining.ResultsCompared with the control group, the expression levels of Nrf2 and CD206 protein in the anterior vaginal wall tissues of the POP groups were significantly decreased (P < 0.05), and were negatively proportional to the degree of prolapse (P < 0.05). The expression of iNOS was significantly increased and was directly proportional to the degree of prolapse (P < 0.05). Hematoxylin-eosin staining and Masson trichrome staining showed that the collagen fibers are more sparsely arranged and disordered in the POP group than the control.ConclusionsIn patients with POP, the expression of antioxidant factor Nrf2 is reduced in the vaginal anterior wall tissues and the antioxidant capacity is weakened, leading to the blocked polarization of macrophages and the accumulation of a large number of M1 macrophages in the tissue, affecting the occurrence and development of POP.

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Section: Discussionmentioning

confidence: 99%

“…After acute or subacute injury, oxidative stress will occur in response to adverse stimuli 20 . Nuclear factor-erythroid 2-related factor 2 is a basic leucine zipper that is the major regulatory transcription factor of cellular antioxidant defense system 21 .…”

Section: Discussionmentioning

confidence: 99%

Effect of Nrf2 on Phenotype Changes of Macrophages in the Anterior Vaginal Wall of Women With Pelvic Organ Prolapse

Liu

Chen

et al. 2022

Female Pelvic Med Reconstr Surg

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“…Fibroblasts represent the most abundant cell type in the uterosacral ligament and other pelvic connective tissues, which help provide mechanical support to pelvic organs. Primary fibroblasts have been isolated from pelvic connective tissues to investigate the pathogenesis of POP ( 29 , 30 ), as their functional changes under mechanical stress or other pathological conditions contribute to the development of POP ( 8 , 31 ). Fibroblasts have been found to exhibit impaired cell contractility ( 32 ), reduced cell attachment ( 33 ), delayed mechanical responses ( 34 ), increased apoptosis ( 35 ), and altered ECM protein production ( 33 ) in POP compared to fibroblasts in non-POP.…”

Section: Discussionmentioning

confidence: 99%

CD106/VCAM-1 distinguishes a fibroblast subpopulation with high colony-forming capacity and distinct protein expression from the uterosacral ligament

Sima

Xiao

et al. 2022

Ann Transl Med

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Background Pelvic organ prolapse (POP) is a common degenerative disease in women which may diminish quality of life. Investigating the pathological changes of the uterosacral ligament, including the functional changes of fibroblasts, is critical to understanding the pathophysiology of POP. This study was designed to isolate CD106-positive (CD106 + ) fibroblasts from the human uterosacral ligament and assess the function and expression of this subpopulation. Methods We separated CD106 + fibroblasts and CD106 negative (CD106 − ) fibroblasts by fluorescence-activated cell sorting (FACS) and cultured them for subsequent experiments. Flow cytometric analysis was used to test the sorting efficiency, CD106 expression, and typical mesenchymal stem cell (MSC) phenotype marker expression. A colony-forming unit (CFU) assay was applied to evaluate the colony-forming ability of the fibroblasts. Trilineage differentiation capacities were assessed after in vitro induction. The protein levels of vimentin, fibroblast specific protein-1 (FSP-1), collagen I (COL 1), matrix metallopeptidase-1 (MMP-1), and α-smooth muscle actin (α-SMA) were detected by western blot analysis. The expression of CD106 was verified by flow cytometric analysis and immunohistochemistry (IHC) in the POP and non-POP groups. Results The CD106 + fibroblasts were isolated with a purity of (93.50±3.91)%. The CD106 + fibroblasts exhibited higher colony-forming capacity than that of CD106 − fibroblasts, but neither of them showed adipogenic or osteogenic differentiation similar to that of MSCs. The protein levels of MMP-1 and α-SMA were lower, and the level of COL 1 was higher in the CD106 + fibroblasts than in the CD106− fibroblasts. In addition, we observed a decreased expression of CD106 in the POP group compared with the non-POP group. Conclusions Our results suggest that CD106 + fibroblasts possess a high colony-forming capacity and distinct protein expression, and this subpopulation is reduced in POP.

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“…The pathogenesis of POP associated with increasing age is influenced by the aging process in general and the aging of all fibroblasts in the pelvic tissue. Mechanisms leading to the aging of fibroblasts may include gene instability and mitochondrial dysfunction [24].…”

Section: Discussionmentioning

confidence: 99%

The Matrix Metaloproteinase-1 Gene Polymorphisms as Risk Factor of Pelvic Organ Prolapse in Balinese Woman

Santoso

Putra

Megadhana

et al. 2022

EJMED

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Pelvic organ prolapse (POP) is a gynecological problem that can worsen the psychosocial, economic, and sexual function of women and often relapses after surgery. POP is associated with weakness of the pelvic floor supporting structures. Pelvic organ prolapse is associated with a reduced quality of life for millions of women worldwide. The purpose of this study was to determine the role of the MMP-1 rs 1799750 gene polymorphisms as a risk factor for pelvic organ prolapse in Balinese women. This observational case-control study involves 30 patients with pelvic organ prolapse as the case group and 30 patients without pelvic organ prolapse as the control group. The study was conducted at the Integrated Biomedical Laboratory, Faculty of Medicine, Udayana University. Three milliliters of venous blood samples were taken from each patient and DNA examination was performed to determine MMP-1 gene polymorphisms. Risk assessment of the MMP-1 gene polymorphism for pelvic organ prolapse was done by controlling for confounding variables, including age, parity, heavy work, body mass index, menopausal status, and history of hysterectomy, through multivariate logistic regression conditional test. Result from this study is the MMP-1 gene polymorphism increased the risk of pelvic organ prolapse 4.33 times compared to non-prolapsed in Balinese women (OR 4.33, 95%CI 1.20 -15.61, p = 0.020). After controlling for various confounding variables, MMP-1 gene polymorphism still increased the risk of pelvic organ prolapse up to 5.52 times (AOR 5.52, 95%CI 1.352-22.50, p = 0.02). Conclusion from this study is MMP-1 gene polymorphism significantly increases the risk of pelvic organ prolapse in Balinese women.

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Cellular senescence: A pathogenic mechanism of pelvic organ prolapse (Review)

Cited by 25 publications

References 81 publications

Effect of Nrf2 on Phenotype Changes of Macrophages in the Anterior Vaginal Wall of Women With Pelvic Organ Prolapse

Effect of Nrf2 on Phenotype Changes of Macrophages in the Anterior Vaginal Wall of Women With Pelvic Organ Prolapse

CD106/VCAM-1 distinguishes a fibroblast subpopulation with high colony-forming capacity and distinct protein expression from the uterosacral ligament

The Matrix Metaloproteinase-1 Gene Polymorphisms as Risk Factor of Pelvic Organ Prolapse in Balinese Woman

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