The Experts below are selected from a list of 81 Experts worldwide ranked by ideXlab platform

Lee Roth - One of the best experts on this subject based on the ideXlab platform.

  • a new role of the membrane type Matrix Metalloproteinase 16 mmp16 mt3 mmp in neural crest cell migration
    The International Journal of Developmental Biology, 2017
    Co-Authors: Lee Roth, Rotem Kalevaltman, Efrat Monsonegoornan, Dalit Seladonenfeld
    Abstract:

    Neural crest cells (NCCs) are a transient population of neuroectodermal-originated cells that populate the dorsal neural tube (dNT), before migrating and giving rise to multiple cell lineages in the developing embryo. Prior to their migration, NCCs undergo epithelial-to-mesenchymal-transition (EMT) through which they lose cell contacts and detach from the dNT to invade their surrounding environment. Multiple signals and transcription factors have been identified to regulate these events. Yet, less is known regarding effectors that act downstream to execute the actual NCC separation and migration. Matrix Metalloproteinases (MMPs) are a family of proteases that degrade the extracellular Matrix as well as other pericellular proteins during processes of tissue remodeling, angiogenesis and metastasis. Previously, we and others have demonstrated the role of the gelatinases MMP2 and MMP9 during the onset of NCC migration. Several evidences link the cleavage and activation of these secreted gelatinases to the activity of membrane-type MMPs (MT-MMP), such as MMP14 and MMP16, which are tethered to plasma membrane and affect various cellular behaviors. The aim of this study was to investigate whether MMP16 acts in NCCs. Here we demonstrate the expression of MMP16 mRNA and protein in cranial NCCs in avian embryos. Knockdown of MMP16 inhibited NCC migration. This inhibition was rescued by the addition of recombinant MMP16, which was also sufficient to increase proper NCC migration. Furthermore, excess MMP16 caused enhanced NCC EMT, concomitant with degradation of dNT-related proteins, laminin and N-cadherin. Altogether, these results uncover MMP16 as a new effector participating in EMT and in the migration of NCCs.

  • A new role of the membrane-type Matrix Metalloproteinase 16 (MMP16/MT3-MMP) in neural crest cell migration.
    The International journal of developmental biology, 2017
    Co-Authors: Lee Roth, Rotem Kalev-altman, Efrat Monsonego-ornan, Dalit Sela-donenfeld
    Abstract:

    Neural crest cells (NCCs) are a transient population of neuroectodermal-originated cells that populate the dorsal neural tube (dNT), before migrating and giving rise to multiple cell lineages in the developing embryo. Prior to their migration, NCCs undergo epithelial-to-mesenchymal-transition (EMT) through which they lose cell contacts and detach from the dNT to invade their surrounding environment. Multiple signals and transcription factors have been identified to regulate these events. Yet, less is known regarding effectors that act downstream to execute the actual NCC separation and migration. Matrix Metalloproteinases (MMPs) are a family of proteases that degrade the extracellular Matrix as well as other pericellular proteins during processes of tissue remodeling, angiogenesis and metastasis. Previously, we and others have demonstrated the role of the gelatinases MMP2 and MMP9 during the onset of NCC migration. Several evidences link the cleavage and activation of these secreted gelatinases to the activity of membrane-type MMPs (MT-MMP), such as MMP14 and MMP16, which are tethered to plasma membrane and affect various cellular behaviors. The aim of this study was to investigate whether MMP16 acts in NCCs. Here we demonstrate the expression of MMP16 mRNA and protein in cranial NCCs in avian embryos. Knockdown of MMP16 inhibited NCC migration. This inhibition was rescued by the addition of recombinant MMP16, which was also sufficient to increase proper NCC migration. Furthermore, excess MMP16 caused enhanced NCC EMT, concomitant with degradation of dNT-related proteins, laminin and N-cadherin. Altogether, these results uncover MMP16 as a new effector participating in EMT and in the migration of NCCs.

Dalit Seladonenfeld - One of the best experts on this subject based on the ideXlab platform.

  • a new role of the membrane type Matrix Metalloproteinase 16 mmp16 mt3 mmp in neural crest cell migration
    The International Journal of Developmental Biology, 2017
    Co-Authors: Lee Roth, Rotem Kalevaltman, Efrat Monsonegoornan, Dalit Seladonenfeld
    Abstract:

    Neural crest cells (NCCs) are a transient population of neuroectodermal-originated cells that populate the dorsal neural tube (dNT), before migrating and giving rise to multiple cell lineages in the developing embryo. Prior to their migration, NCCs undergo epithelial-to-mesenchymal-transition (EMT) through which they lose cell contacts and detach from the dNT to invade their surrounding environment. Multiple signals and transcription factors have been identified to regulate these events. Yet, less is known regarding effectors that act downstream to execute the actual NCC separation and migration. Matrix Metalloproteinases (MMPs) are a family of proteases that degrade the extracellular Matrix as well as other pericellular proteins during processes of tissue remodeling, angiogenesis and metastasis. Previously, we and others have demonstrated the role of the gelatinases MMP2 and MMP9 during the onset of NCC migration. Several evidences link the cleavage and activation of these secreted gelatinases to the activity of membrane-type MMPs (MT-MMP), such as MMP14 and MMP16, which are tethered to plasma membrane and affect various cellular behaviors. The aim of this study was to investigate whether MMP16 acts in NCCs. Here we demonstrate the expression of MMP16 mRNA and protein in cranial NCCs in avian embryos. Knockdown of MMP16 inhibited NCC migration. This inhibition was rescued by the addition of recombinant MMP16, which was also sufficient to increase proper NCC migration. Furthermore, excess MMP16 caused enhanced NCC EMT, concomitant with degradation of dNT-related proteins, laminin and N-cadherin. Altogether, these results uncover MMP16 as a new effector participating in EMT and in the migration of NCCs.

Dalit Sela-donenfeld - One of the best experts on this subject based on the ideXlab platform.

  • A new role of the membrane-type Matrix Metalloproteinase 16 (MMP16/MT3-MMP) in neural crest cell migration.
    The International journal of developmental biology, 2017
    Co-Authors: Lee Roth, Rotem Kalev-altman, Efrat Monsonego-ornan, Dalit Sela-donenfeld
    Abstract:

    Neural crest cells (NCCs) are a transient population of neuroectodermal-originated cells that populate the dorsal neural tube (dNT), before migrating and giving rise to multiple cell lineages in the developing embryo. Prior to their migration, NCCs undergo epithelial-to-mesenchymal-transition (EMT) through which they lose cell contacts and detach from the dNT to invade their surrounding environment. Multiple signals and transcription factors have been identified to regulate these events. Yet, less is known regarding effectors that act downstream to execute the actual NCC separation and migration. Matrix Metalloproteinases (MMPs) are a family of proteases that degrade the extracellular Matrix as well as other pericellular proteins during processes of tissue remodeling, angiogenesis and metastasis. Previously, we and others have demonstrated the role of the gelatinases MMP2 and MMP9 during the onset of NCC migration. Several evidences link the cleavage and activation of these secreted gelatinases to the activity of membrane-type MMPs (MT-MMP), such as MMP14 and MMP16, which are tethered to plasma membrane and affect various cellular behaviors. The aim of this study was to investigate whether MMP16 acts in NCCs. Here we demonstrate the expression of MMP16 mRNA and protein in cranial NCCs in avian embryos. Knockdown of MMP16 inhibited NCC migration. This inhibition was rescued by the addition of recombinant MMP16, which was also sufficient to increase proper NCC migration. Furthermore, excess MMP16 caused enhanced NCC EMT, concomitant with degradation of dNT-related proteins, laminin and N-cadherin. Altogether, these results uncover MMP16 as a new effector participating in EMT and in the migration of NCCs.

Michael W. Crowder - One of the best experts on this subject based on the ideXlab platform.

  • Biochemical and spectroscopic characterization of the catalytic domain of MMP16 (cdMMP16)
    JBIC Journal of Biological Inorganic Chemistry, 2016
    Co-Authors: Fan Meng, Hao Yang, Mahesh Aitha, Sam George, David L. Tierney, Michael W. Crowder
    Abstract:

    Membrane-bound Matrix Metalloproteinase 16 (MMP16/MT3-MMP) is considered a drug target due to its role(s) in disease processes such as cancer and inflammation. Biochemical characterization of MMP16 is critical for developing new generation MMP inhibitors (MMPi), which exhibit high efficacies and selectivities. Herein, a modified over-expression and purification protocol was used to prepare the catalytic domain of MMP16 (cdMMP16). The resulting recombinant enzyme exhibited steady-state kinetic constants of K _m = 10.6 ± 0.7 μM and k _cat = 1.14 ± 0.02 s^−1, when using FS-6 as substrate, and the enzyme bound 1.8 ± 0.1 eq of Zn(II). The enzymatic activity of cdMMP16 is salt concentration-dependent, and cdMMP16 exhibits autoproteolytic activity under certain conditions, which may be related to an in vivo regulatory mechanism of MMP16 and of other membrane-type MMPs (MT-MMPs). Co(II)-substituted analogs (Co_2- and ZnCo) of cdMMP16 were prepared and characterized using several spectroscopic techniques, such as UV–Vis, ^1H NMR, and EXAFS spectroscopies. A well-characterized cdMMP16 is now available for future inhibitor screening efforts.

  • Biochemical and spectroscopic characterization of the catalytic domain of MMP16 (cdMMP16)
    JBIC Journal of Biological Inorganic Chemistry, 2016
    Co-Authors: Fan Meng, Hao Yang, Mahesh Aitha, Sam George, David L. Tierney, Michael W. Crowder
    Abstract:

    Membrane-bound Matrix Metalloproteinase 16 (MMP16/MT3-MMP) is considered a drug target due to its role(s) in disease processes such as cancer and inflammation. Biochemical characterization of MMP16 is critical for developing new generation MMP inhibitors (MMPi), which exhibit high efficacies and selectivities. Herein, a modified over-expression and purification protocol was used to prepare the catalytic domain of MMP16 (cdMMP16). The resulting recombinant enzyme exhibited steady-state kinetic constants of K _m = 10.6 ± 0.7 μM and k _cat = 1.14 ± 0.02 s^−1, when using FS-6 as substrate, and the enzyme bound 1.8 ± 0.1 eq of Zn(II). The enzymatic activity of cdMMP16 is salt concentration-dependent, and cdMMP16 exhibits autoproteolytic activity under certain conditions, which may be related to an in vivo regulatory mechanism of MMP16 and of other membrane-type MMPs (MT-MMPs). Co(II)-substituted analogs (Co_2- and ZnCo) of cdMMP16 were prepared and characterized using several spectroscopic techniques, such as UV–Vis, ^1H NMR, and EXAFS spectroscopies. A well-characterized cdMMP16 is now available for future inhibitor screening efforts.

Victor W.m. Van Hinsbergh - One of the best experts on this subject based on the ideXlab platform.

  • Involvement of Membrane-Type Matrix Metalloproteinases (MT-MMPs) in Capillary Tube Formation by Human Endometrial Microvascular Endothelial Cells: Role of MT3-MMP
    The Journal of clinical endocrinology and metabolism, 2004
    Co-Authors: Margreet Plaisier, Kitty Kapiteijn, Pieter Koolwijk, Catherine Fijten, Roeland Hanemaaijer, Jos M. Grimbergen, Adri Mulder-stapel, Paul H.a. Quax, Frans M. Helmerhorst, Victor W.m. Van Hinsbergh
    Abstract:

    In the endometrium, angiogenesis is a physiological process, whereas in most adult tissues neovascularization is initiated only during tissue repair or pathological conditions. Pericellular proteolysis plays an important role in angiogenesis being required for endothelial cell migration, invasion, and tube formation. We studied the expression of proteases by human endometrial microvascular endothelial cells (hEMVECs) and their involvement in the formation of capillary tubes and compared these requirements with those of foreskin MVECs (hFMVECs). Inhibition of urokinase and Matrix Metalloproteinase (MMP) both reduced tube formation in a fibrin or fibrin/collagen Matrix. hEMVECs expressed various MMP mRNAs and proteins; in particular MMP-1, MMP-2, and membrane-type (MT)1-, MT3-, and MT4-MMPs. MT3- and MT4-MMP mRNA expressions were significantly higher in hEMVECs than in hFMVECs. Other MT-MMP mRNAs and MMP-9 were hardly detectable. Immunohistochemistry confirmed the presence of MT3-MMP in endothelial cells of endometrial tissue. Overexpression of tissue inhibitor of MMP (TIMP)-1 or TIMP-3 by adenoviral transduction of hEMVECs reduced tube formation to the same extent, whereas only TIMP-3 was able to inhibit tube formation by hFMVECs. Tube formation by hEMVECs was partly inhibited by the presence of anti-MT3-MMP IgG. Thus, in contrast to tube formation by hFMVECs, which largely depends on MT1-MMP, capillary-like tube formation by hEMVECs is, at least in part, regulated by MT3-MMP. Chemicals / CAS: collagen, 9007-34-5; fibrin, 9001-31-4; gelatinase A, 146480-35-5; immunoglobulin G, 97794-27-9; interstitial collagenase, 9001-12-1; tissue inhibitor of Metalloproteinase 1, 140208-24-8; tissue inhibitor of Metalloproteinase 3, 145809-21-8, 164781-40-2; urokinase, 139639-24-0; Collagen Type I; Matrix Metalloproteinase 16, EC 3.4.24.-; Matrix Metalloproteinases, Membrane-Associated, EC 3.4.24.-; Metalloendopeptidases, EC 3.4.24.-; MMP16 protein, human; Plasmin, EC 3.4.21.7; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-3; Urinary Plasminogen Activator, EC 3.4.21.73