Increased matrix metalloproteinases-1,-9 in the uterosacral ligaments and vaginal tissue from women with pelvic organ prolapse

Dviri, Michal; Leron, Elad; Dreiher, Jacob; Mazor, Moshe; Shaco‐Levy, Ruthy

doi:10.1016/j.ejogrb.2010.12.043

Cited by 49 publications

(56 citation statements)

References 21 publications

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“…Gabriel et al (28) reported that an increased MMP-2 expression in USL correlated with the incidence of POP. Dviri et al (29) found higher expression levels of MMP-1/9 in vaginal wall biopsies from women with POP compared with the controls. To analyze the reasons for discrepancies in the above-mentioned findings, firstly, the effects of confounding factors, such as age, parity, obesity, menopausal status and a history of HRT should be considered.…”

Section: Discussionmentioning

confidence: 99%

Role of transforming growth factor β-1 in the pathogenesis of pelvic organ prolapse: A potential therapeutic target

Liu

Wang

et al. 2017

International Journal of Molecular Medicine

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The present study aimed to reveal the metabolic alterations of the extracellular matrix (ECM) in uterosacral ligament (USL) with pelvic organ prolapse (POP) and to explore the role of transforming growth factor-β1 (TGF-β1) in pathogenesis of POP. For this purpse, 60 participants who underwent hysterectomy for benign indications were enrolled, 30 of which had symptomatic POP (grade II, III or IV) and composed the POP group, and the other 30 had asymptomatic POP (grade I or less) and served as the controls. Collagen fibers, elastin, matrix metalloproteinase (MMP)-2/9, tissue inhibitor of matrix metalloproteinases (TIMP)-2 and TGF-β1 were examined by Masson's trichrome staining, immunohistochemistry and RT-qPCR using USL biopsies. In vitro, human USL fibroblasts (hUSLFs) were primary cultured, pre-treated with recombinant TGF-β1 (0, 5, or 10 ng/ml) and then subjected to cyclic mechanical stretching (CMS; 0 or 5,333 με strain). Changes in the expression levels of collagen type I/III, elastin, TIMP-2, MMP-2/9 and Smad were detected. Our results revealed that at the tissue level, the expression of collagen fibers, elastin, TIMP-2 and TGF-β1 was significantly reduced in the POP group, while the activities of MMP-2/9 were significantly upregulated, compared with the control group. Statistical analysis indicated that the mRNA expression of TGF-β1 inversely correlated with the severity of POP partially. Our in vitro experimental data demonstrated that a CMS of 5333 με strain promoted the degradation of ECM proteins, inhibited the synthesis of TIMP-2, and upregulated the proteolytic activities of MMP-2/9. Pre-treatment with TGF-β1 attenuated the loss of ECM by stimulating the synthesis of TIMP-2 and inhibiting the activities of MMP-2/9 through the TGF-β1/Smad3 signaling pathway. On the whole, our data indicate that the reduced anabolism and increased catabolism of ECM proteins in USL are the pathological characteristics of POP. TGF-β1 not only has a specific value in predicting the severity of POP, but should also be considered as a novel therapeutic target for POP.

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Section: Discussionmentioning

confidence: 99%

Role of transforming growth factor β-1 in the pathogenesis of pelvic organ prolapse: A potential therapeutic target

Liu

Wang

et al. 2017

International Journal of Molecular Medicine

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“…Gabriel et al [7] found an increased MMP2 expression in the uterosacral ligaments of patients with POP, and Jackson et al [30] examining the vaginal epithelium of eight premenopausal women with prolapse (with and without urinary incontinence) and the same tissue of ten subjects without the disease found a decrease in total collagen content and an increase in MMPs expression in the former group. Recently, it has been also demonstrated an increased expression of MMP-1 and -9 in the uterosacral ligaments and vaginal tissue of women with POP [8,9].…”

Section: Discussionmentioning

confidence: 99%

“…MMP-9 and MMP-3 are stromelysins (gelatinase-B and stromelysin-1) whose substrata are proteoglycans, laminin and fibronectin that are mainly present in vessels and in pelvic tissue. It has been recently demonstrated by immunohistochemistry that in uterosacral ligaments and in vaginal tissue of women with POP there is an increased expression of MMP-1, MMP-2 and MMP-9 [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Type I collagen and matrix metalloproteinase 1, 3 and 9 gene polymorphisms in the predisposition to pelvic organ prolapse

Ferrari

Rossi²,

Biondi³

et al. 2011

Arch Gynecol Obstet

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“…Dviri et al showed an increase in both MMP-1 and MMP-9 expression in uterosacral ligaments in women with POP [18]. Conversely, Phillips et al showed no difference in expression of MMP-9 in uterosacral ligaments in women with POP compared to controls [19].…”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor β1 and Extracellular Matrix Protease Expression in the Uterosacral Ligaments of Patients With and Without Pelvic Organ Prolapse

Leegant

Zuckerwise

Downing³

et al. 2015

Female Pelvic Medicine &Amp; Reconstructive Surgery

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Objectives This study was undertaken to evaluate the expression of transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase 9 (MMP-9), key regulators of the extracellular matrix composition, in the uterosacral ligaments (USL) of women with pelvic organ prolapse compared with controls. Methods Under IRB approval, USL samples were obtained from women undergoing vaginal hysterectomy for stage two or greater pelvic organ prolapse (cases, n=21) and from women without pelvic organ prolapse undergoing vaginal hysterectomy for benign indications (controls, n=19). Hematoxylin and eosin and trichrome staining were performed on the USL sections, and the distribution of smooth muscle and fibrous tissue quantified. Immunohistochemical staining was performed using anti-TGF-β1 and anti-MMP-9 antibodies. The expression of TGF-β1 and MMP-9 was evaluated by the pathologist, who was blinded to all clinical data. Results TGF-β1 expression positively correlated with MMP-9 expression (R=0.4, P=0.01). The expression of TGF-β1 and MMP-9 were similar in subjects with pelvic organ prolapse versus controls. There was a significant increase in fibrous tissue (P=0.008), and a corresponding decrease in smooth muscle (P=0.03), associated with increasing age. TGF-β1 expression, but not MMP-9 expression, also significantly increased with age (P=0.02). Discussion Although our study uncovered age-related alterations in USL composition and TGF-β1 expression, there was no difference in the expression of TGF-β1 or MMP-9 in the subjects with pelvic organ prolapse versus controls.

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Increased matrix metalloproteinases-1,-9 in the uterosacral ligaments and vaginal tissue from women with pelvic organ prolapse

Cited by 49 publications

References 21 publications

Role of transforming growth factor β-1 in the pathogenesis of pelvic organ prolapse: A potential therapeutic target

Role of transforming growth factor β-1 in the pathogenesis of pelvic organ prolapse: A potential therapeutic target

Type I collagen and matrix metalloproteinase 1, 3 and 9 gene polymorphisms in the predisposition to pelvic organ prolapse

Transforming Growth Factor β1 and Extracellular Matrix Protease Expression in the Uterosacral Ligaments of Patients With and Without Pelvic Organ Prolapse

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