Secretion of tissue inhibitors of matrix metalloproteinases by human fetal membranes, decidua and placenta at parturition

At parturition, breakdown of extracellular matrix in the fetal membranes may play a part in the rupture of the membranes and in the aetiology of premature rupture, in addition to having a regulatory role in the cell-cell interactions and signalling at the feto-maternal interface to stimulate myometrial contractility. The matrix metalloproteinases (MMPs) are important enzymes for the breakdown of extracellular matrix and their activity is regulated by a family of endogenous inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs). At parturition, alteration in the balance between MMPs and TIMPs may mediate this extracellular matrix breakdown during rupture of fetal membranes. The aims of this study were to determine if the intrauterine secretion of TIMPs changes at labour, and to characterise their cellular sources. A broad range of TIMP activities (27-30 kDa, 24 kDa and 21 kDa) were detected by reverse zymography in term amniotic fluid. There was a significant (P<0.05) decrease in the amount of TIMPs in amniotic fluid and their release with the onset of labour. The TIMPs were characterised by immunoblot as TIMPs-1, -2, -3 and -4. High levels of TIMPs were secreted by explants of chorio-decidua, decidua parietalis and placenta, with less being released by amnion. Immunolocalisation studies revealed a specific distribution pattern for each of the TIMP isoforms. Trophoblast cells of chorion laeve, decidua parietalis and placental syncytiotrophoblast demonstrated specific immunoreactivity for all four isoforms. TIMPs were also found bound to selective regions of extracellular matrix. The decrease in TIMPs during labour may permit increased breakdown of extracellular matrix in the fetal membranes and decidua at parturition, thus altering cell signalling at the feto-maternal interface and facilitating membrane rupture.

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The Unwounded Skin Remodeling in Animal Models of Diabetes Types 1 and 2

Physiological Research ◽

10.33549/physiolres.932534 ◽

2013 ◽

pp. 519-526 ◽

Cited By ~ 8

Author(s):

M. KNAŚ ◽

M. NICZYPORUK ◽

A. ZALEWSKA ◽

H. CAR

Keyword(s):

Extracellular Matrix ◽

Matrix Metalloproteinases ◽

Diabetes Type ◽

Tissue Inhibitor Of Metalloproteinase ◽

Tissue Inhibitors Of Metalloproteinases ◽

Control Group ◽

Diabetes Type 1 ◽

Tissue Inhibitors ◽

The Matrix

Diabetes mellitus types 1 and 2 are chronic diseases that cause serious health complications, including dermatologic problems. The diabetic skin is characterized by disturbances in collagen metabolism. A tissue remodeling depends on the degradation of extracellular matrix through the matrix metalloproteinases, which are regulated by e.g. the tissue inhibitors of metalloproteinases. The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is essential to maintain homeostasis in the skin. The aim of this study was to determine the concentration of metalloproteinase 2, tissue inhibitor of metalloproteinase 3 and the concentration of collagen type 1 in unwounded skin of diabetes type 1 and 2 and healthy controls. The treatment of diabetes resulted in a significant decrease of MMP2, increase of TIMP3 and COL1 concentrations in the skin as compared to the untreated diabetic skin. The concentrations of MMP2 in the skin of treated rats did not show significant differences from the healthy control group. TIMP3 concentrations in the skin of treated rats are not returned to the level observed in the control group. Disturbances of the extracellular matrix of the skin are similar in diabetes type 1 and 2. Application of insulin in diabetes therapy more preferably affects the extracellular matrix homeostasis of the skin.

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Expression of Matrix Metalloproteinase (MMP)-2 and MMP-9 in Human Placenta and Fetal Membranes in Relation to Preterm and Term Labor

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.87.3.8320 ◽

2002 ◽

Vol 87 (3) ◽

pp. 1353-1361 ◽

Cited By ~ 114

Author(s):

Ping Xu ◽

Nadia Alfaidy ◽

John R. G. Challis

Keyword(s):

Cervical Ripening ◽

Fetal Membrane ◽

Fetal Membranes ◽

Trophoblast Cells ◽

Specific Expression ◽

Membrane Rupture ◽

Specific Distribution ◽

Significant Difference ◽

Chorion Laeve ◽

Term Labor

Extensive extracellular matrix (ECM) remodeling is found in many processes during human parturition at term and preterm. These include cervical ripening, fetal membrane rupture, and placental detachment from the maternal uterus. Matrix metalloproteinases (MMPs) are the main mediators of ECM degradation. The present study was designed to investigate the expression of MMP-2 and MMP-9 in human fetal membranes (FMs) and placental (PL) tissues with or without labor at preterm and term parturition. Both zymography and Western blot analysis showed that MMP-9 was significantly (P < 0.01) increased in preterm and term labor FM, compared with nonlabor. Term labor PL also had a much higher (P < 0.05) level of MMP-9 than that of term nonlabor. No significant difference in MMP-2 expression was found between labor and nonlabor tissues. Immunolocalization studies revealed a specific distribution pattern for MMP-2 and MMP-9. MMP-2 was localized to the amnion mesenchyme, chorion laeve trophoblast, decidua parietalis, and blood vessels in PL villi. MMP-9 was localized mainly to amnion epithelia, chorion laeve trophoblast, decidua parietalis, and PL syncytiotrophoblasts. Separate cell culture from different layers of FM and culture of purified PL trophoblast cells showed that PL syncytiotrophoblast and amnion epithelial cells exclusively produced MMP-9; chorion trophoblast cells secreted both MMP-2 and MMP-9, but amnion mesenchymal cells produced only MMP-2. We concluded that MMP-2 and MMP-9 exhibited cell-specific expression in the human PL. An increase in MMP-9 expression may contribute to degradation of the ECM in the FM and PL, thereby facilitating FM rupture and PL detachment from the maternal uterus at labor, both preterm and term.

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Matrix metalloproteinases-2 and -9 and their endogenous tissue inhibitors in tissue remodeling after sealing of the fetal membranes in a sheep model of fetoscopic surgery

Journal of the Society for Gynecologic Investigation ◽

10.1016/s1071-5576(02)00142-9 ◽

2002 ◽

Vol 9 (3) ◽

pp. 137-145 ◽

Cited By ~ 13

Author(s):

R Devlieger

Keyword(s):

Matrix Metalloproteinases ◽

Tissue Remodeling ◽

Fetal Membranes ◽

Sheep Model ◽

Tissue Inhibitors

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Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

Critical Reviews in Oral Biology & Medicine ◽

10.1177/10454411010120050201 ◽

2001 ◽

Vol 12 (5) ◽

pp. 373-398 ◽

Cited By ~ 144

Author(s):

Bjorn Steffensen ◽

Lari Häkkinen ◽

Hannu Larjava

Keyword(s):

Extracellular Matrix ◽

Wound Healing ◽

Matrix Metalloproteinases ◽

Wound Repair ◽

Enzyme Activation ◽

Processing Enzymes ◽

The Matrix ◽

Signaling Receptors ◽

State Of Rest ◽

And Function

During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.

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Temporal changes in myocardial collagen, matrix metalloproteinases, and their tissue inhibitors in the left ventricular myocardium in experimental chronic mitral regurgitation in rodents

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00099.2018 ◽

2018 ◽

Vol 315 (5) ◽

pp. H1269-H1278 ◽

Cited By ~ 5

Author(s):

Daniella Corporan ◽

Daisuke Onohara ◽

Roberto Hernandez-Merlo ◽

Alicja Sielicka ◽

Muralidhar Padala

Keyword(s):

Extracellular Matrix ◽

Matrix Metalloproteinases ◽

Mitral Regurgitation ◽

Temporal Changes ◽

Left Ventricular ◽

Human Condition ◽

Ventricular Dilatation ◽

Mitral Leaflet ◽

Tissue Inhibitors ◽

Myocardial Collagen

Mitral regurgitation (MR) imposes left ventricular volume overload, triggering rapid ventricular dilatation, increased myocardial compliance, and, ultimately, cardiac dysfunction. Breakdown of the extracellular matrix has been hypothesized to drive these rapid changes, partially from an imbalance in the matrix metalloproteinases (MMPs) and their tissue inhibitors [tissue inhibitors of metalloproteinase (TIMPs)]. In the present study, we developed a rat model of severe MR that mimics the human condition and investigated the temporal changes in extracellular matrix-related genes, collagen biosynthesis proteins, and proteolytic enzymes over a 20-wk period. Male Sprague-Dawley rats were anesthetized to a surgical plane with mechanical ventilation, and a thoracotomy was performed to expose the apex. Using transesophageal ultrasound guidance, a needle was inserted into the beating heart to perforate the anterior mitral leaflet and create severe MR. Animals were survived for 20 wk, with some animals terminated at 2, 10, and 20 wk for analysis of left ventricular tissue. A sham group that underwent the same surgery without mitral leaflet perforation and MR were used as controls. At 2 wk post-MR, increased collagen gene expression was measured, but protein levels of collagen did not corroborate this finding. In parallel, MMP-1-to-TIMP-4, MMP-2-to-TIMP-1, and MMP-2-to-TIMP-3 ratios were significantly elevated, indicating a proteolytic milieu in the myocardium, possibly causing collagen degradation. By 20 wk, many of the initial differences seen in the proteolytic ratios were not observed, with an increase in collagen compared with the 2-wk time point. Altogether, this data indicates that an imbalance in the MMP-to-TIMP ratio may occur early and potentially contribute to the early dilatation and compliance observed structurally. NEW & NOTEWORTHY In this rodent model of severe mitral regurgitation that mimics the human condition, eccentric left ventricular dilatation occurred rapidly and persisted over the 20-wk period with parallel changes in myocardial collagen and matrix metalloproteinases that may drive the extracellular matrix breakdown.

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Expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases, and extracellular matrix mRNA following exposure to mineral fibers and cigarette smoke in vivo.

Environmental Health Perspectives ◽

10.1289/ehp.97105s51247 ◽

1997 ◽

Vol 105 (suppl 5) ◽

pp. 1247-1251 ◽

Cited By ~ 22

Author(s):

Y Morimoto ◽

T Tsuda ◽

H Nakamura ◽

H Hori ◽

H Yamato ◽

...

Keyword(s):

Extracellular Matrix ◽

Matrix Metalloproteinases ◽

Cigarette Smoke ◽

Tissue Inhibitors Of Metalloproteinases ◽

Tissue Inhibitors ◽

Mineral Fibers

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Molecular regulation of cellular invasion— role of gelatinase A and TIMP-2

Biochemistry and Cell Biology ◽

10.1139/o96-088 ◽

1996 ◽

Vol 74 (6) ◽

pp. 823-831 ◽

Cited By ~ 58

Author(s):

Anita E. Yu ◽

Robert E. Hewitt ◽

David E. Kleiner ◽

William G. Stetler-Stevenson

Keyword(s):

Extracellular Matrix ◽

Matrix Metalloproteinases ◽

Tissue Inhibitors Of Metalloproteinases ◽

Gelatinase A ◽

Cellular Mechanisms ◽

Cell Matrix ◽

Matrix Interactions ◽

The Matrix ◽

Cell Matrix Interactions

Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much of the coordinate (physiological) or discoordinate (pathological) degradation of the ECM is catalyzed by a class of proteases known as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usually secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators and inhibitors. One member of the matrixin family, gelatinase A, is regulated differently from other MMPs, suggesting that it may play a unique role in cell–matrix interactions, including cell invasion. The conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a key event in the acquisition of invasive potential. This discussion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this process.Key words: tissue inhibitors of metalloproteinases, metalloproteinase, gelatinases, extracellular matrix, activation.

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