Matrix metalloproteinases as mediators of reproductive function

Hulboy, Diana L.; Rudolph, Laura A.; Matrisian, Lynn M.

doi:10.1093/molehr/3.1.27

Cited by 413 publications

(288 citation statements)

References 43 publications

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“…MMP2 is an important member of the gelatinase subgroup which mainly digests peptide bonds in denatured collagens (gelatins) to yield small peptides, while MMP3 is a member of the stromelysin subgroup that has a similar domain structure to those of collagenases, but they cannot cleave native fibrillar collagens (Visse & Nagase 2003, Swarnakar et al 2011. MMP3 cleaves a number of substrates including proteoglycans, fibronectins, gelatins, collagen IV, and V (Hulboy et al 1997). A number of studies have suggested that these enzymes have been implicated in the process of parturition, rupture of membranes, and intra amniotic infection (Athayde et al 1999, Maymon et al 2000a, 2000b, 2000c.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites

Sundrani¹,

Chavan‐Gautam²,

Pisal³

et al. 2013

Reproduction

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Maternal nutrition is an important determinant of one-carbon metabolism and defects in the one-carbon metabolism may lead to poor obstetric outcomes. This study was designed to test the hypothesis that altered intake/metabolism of micronutrients (folic acid and vitamin B 12 ) and docosahexaenoic acid (DHA) contributes to increased homocysteine and oxidative stress leading to altered levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in women delivering preterm. We have earlier reported increased vitamin B 12 , homocysteine, and oxidative stress along with reduced placental DHA in women delivering preterm. In this study, we further examine the placental levels of MMP2, MMP3, TIMP1, and TIMP2 in 75 women delivering at term and 73 women delivering preterm. Placental levels of MMPs and TIMPs were determined by ELISA. Placental MMP2 and MMP3 levels were higher (P!0.01) in women delivering preterm as compared with term. There was no difference in the placental TIMP1 and TIMP2 levels in women delivering preterm and at term. Further placental MMP2 and MMP3 levels were higher (P!0.01) in women with preterm labor as compared with those in labor at term, suggesting that MMPs may favor degradation of extracellular matrix in the placenta during preterm labor. Our study for the first time suggests a crucial role of micronutrients and MMPs in preterm birth. Future studies need to examine if epigenetic modifications through the one-carbon cycle contribute to increased levels of MMPs leading to preterm deliveries.

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Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites

Sundrani¹,

Chavan‐Gautam²,

Pisal³

et al. 2013

Reproduction

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“…They showed inhibition of MMP-1 expression using explants of human endometrium (Marbaix et al 1992) and cultured HESCs (Lockwood et al 1998); however, the mechanism of the regulation on transcription of MMP-1 by progesterone is not yet understood. Progesterone may regulate MMP-1 gene via non-classical DNA sequences (Hulboy et al 1997). Furthermore, the ligand-activated progesterone receptor may decrease the amounts of transcription factors by a direct protein-protein interaction, resulting in a decreased binding of the transcription factors on the AP-1 site of MMP-1 promoter (Dong et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Testosterone inhibits matrix metalloproteinase-1 production in human endometrial stromal cells in vitro

Ishikawa¹,

Harada²,

Kubota³

et al. 2007

Reproduction

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Androgen receptor (AR) is reported to be expressed in human uterine endometrium, but not much information is available on the role of androgens in human endometrium. The purpose of this study is to investigate the role of androgens in the regulation of matrix metalloproteinase (MMP)-1, which is one of the important MMPs for menstruation and embryo implantation in human endometrium. Human endometrial stromal cells (HESCs) were obtained from human endometrium by enzymatic dissociation method. Purified HESCs were incubated with 17b-estradiol (E2), testosterone, or E2Ctestosterone. Progestins (natural progesterone or medroxyprogesterone acetate) or vehicle (dimethyl sulfoxide) were also added to the media instead of testosterone. Furthermore, hydroxyflutamide (FLU), a specific AR antagonist, was also supplemented to cultured media. The amounts of MMP-1 in cultured media and in HESC lysates were examined by ELISA measurements and western blotting analysis respectively. The expression of ARmRNA in HESCs RNA was analyzed by RT-PCR. Testosterone significantly inhibited MMP-1 in both cultured media and cell lysates in a dosedependent manner. Progestins also inhibited MMP-1. Furthermore, FLU completely recovered the decrease of MMP-1 induced by testosterone. ARmRNA was detected in all HESCs RNA. The present study demonstrated that the secretion and production of MMP-1 in HESCs in vitro were inhibited by testosterone through androgen receptors in a manner similar to that seen for progesterone. These findings indicate that androgen may play an important role in morphological and functional changes of human endometrium.

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“…6 These proteolytic enzymes are involved in connective tissue remodeling as well as in embryonic growth, ovulation, wound healing and menstruation. 7,8 Moreover, abnormal production of these proteinases is implicated in a number of pathological conditions. 9 It has been shown that CXCL12-CXCR4 interactions may play a role in the metastasis of prostate cancer to bone.…”

mentioning

confidence: 99%

CXCL12–CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion

Singh

Grizzle

et al. 2004

Laboratory Investigation

213

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The mechanisms responsible for prostate cancer metastasis are incompletely understood at both the cellular and molecular levels. In this regard, chemokines are a family of small, cytokine-like proteins that induce motility of neoplastic cells, leukocytes and cancer cells. The current study evaluates the molecular mechanisms of CXCL12 and CXCR4 in prostate cancer cell migration and invasion. We report that functional CXCR4 is significantly expressed by prostate cancer cell lines, LNCaP and PC3, when compared with normal prostatic epithelial cells (PrEC). As measured using motility and invasion chamber assays, prostate cancer cells migrated and invaded through extracellular matrix components in response to CXCL12, at rates that corresponded to CXCR4 expression. Anti-CXCR4 antibodies (Abs) significantly impaired the migration and invasive potential of PC3 and LNCaP cells. CXCL12 induction also enhanced collagenase-1 (metalloproteinase-1 (MMP-1)) expression by LNCaP and PC3 cells. Collagenase-3 (MMP-13) was expressed by prostate cancer cells, but it was not expressed by PrEC cells or modulated by CXCL12. CXCL12 increased MMP-2 expression by LNCaP and PC3; however, MMP-9 expression was elevated only in PC3 cells after CXCL12-CXCR4 ligation. PC3 cells also expressed high levels of stromelysin-1 (MMP-3) after CXCL12 stimulation. CXCL12 also significantly Keywords: chemokine; metastasis; metalloproteinase; stromal cell-derived factor-1; SDF-1 Despite the obvious importance of metastasis, this process remains incompletely understood at both the cellular and molecular levels. 1 Many factors have been implicated in the process of metastasis, but the precise mechanisms for the directional migration of malignant cells into different organs is unknown. [2][3][4] In this regard, chemokines are a super family of small, cytokine-like proteins that inducethrough G-protein-coupled receptor and cytoskeletal rearrangement-the adhesion of neoplastic cells or leukocytes to endothelial cells as well as the directional migration of cancer cells. 5,6 The ability of neoplastic cells to penetrate the basement membrane and then invade the interstitial stroma to initiate the metastatic process is largely mediated by proteolysis. Many proteinases are capable of degrading extracellular matrix (ECM) components, but matrix metalloproteinases (MMPs) appear to be particularly important for matrix degradation. 6 These proteolytic enzymes are involved in connective tissue remodeling as well as in embryonic growth, ovulation, wound healing and menstruation. 7,8 Moreover, abnormal production of these proteinases is implicated in a number of pathological conditions. 9 It has been shown that CXCL12-CXCR4 interactions may play a role in the metastasis of prostate cancer to bone. 10 However, these interactions alone do not explain the metastasis pattern of prostate cancer or the potential for neoplastic prostate cells to migrate and invade other tissues. We have tested the hypothesis that prostate carcinomas use CXCR4-

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Matrix metalloproteinases as mediators of reproductive function

Cited by 413 publications

References 43 publications

Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites

Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites

Testosterone inhibits matrix metalloproteinase-1 production in human endometrial stromal cells in vitro

CXCL12–CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion

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