The Experts below are selected from a list of 1569 Experts worldwide ranked by ideXlab platform

Takashi Muramatsu - One of the best experts on this subject based on the ideXlab platform.

  • Midkine antisense oligodeoxyribonucleotide inhibits renal damage induced by ischemic reperfusion
    Kidney International, 2005
    Co-Authors: Waichi Sato, Kenji Kadomatsu, Yoshifumi Takei, Yukio Yuzawa, Seiichi Matsuo, Takashi Muramatsu
    Abstract:

    Midkine antisense oligodeoxyribonucleotide inhibits renal damage induced by ischemic reperfusion. Background Midkine, a heparin-binding growth factor, is involved in the migration of inflammatory cells. The inflammatory cell migration to the tubulointerstitium of the kidney after ischemia/reperfusion (I/R) injury is attenuated in Midkine gene–deficient mice, resulting in better preservation of the tubulointerstitium compared with wild-type mice. In the present investigation, we planned to evaluate the usefulness of antisense Midkine for the therapy of ischemic renal failure. Methods Midkine antisense phosphorothioate oligodeoxyribonucleotide (ODN) at a dose of 1 mg/kg in saline was intravenously administered to mice 1 day before or after I/R. The kidneys were removed for examination 1, 2, 3, and 7 days after I/R. Results It was rapidly incorporated into proximal tubular epithelial cells, and inhibited Midkine synthesis, leading to reduced migration of inflammatory cells to the injured epithelial layer. Consequently, the Midkine antisense ODN-treated animals exhibited less severe renal damage than untreated or Midkine sense ODN-treated animals 2 days after I/R as assessed by morphologic criteria and blood urea nitrogen (BUN) and serum creatinine levels. Midkine expression, BUN, and serum creatinine levels were not significantly different between injection of Midkine antisense ODN before and after ischemic injury. Conclusion These results indicate that intravenous injection of Midkine antisense ODN is a candidate for a novel therapeutic strategy against acute tubulointerstitial injury induced by I/R injury.

  • Midkine a heparin binding growth factor promotes growth and glycosaminoglycan synthesis of endothelial cells through its action on smooth muscle cells in an artificial blood vessel model
    Journal of Cell Science, 2002
    Co-Authors: Yukio Sumi, Yoshifumi Takei, Hisako Muramatsu, Kenichiro Hata, Minoru Ueda, Takashi Muramatsu
    Abstract:

    To study the interactions between smooth muscle cells and endothelial cells in vitro, we developed an artificial blood vessel model, which consisted of collagen gel containing human aortic smooth muscle cells and human umbilical vein endothelial cells grown on the gel. The blood vessel model was utilized to investigate the role of Midkine, a heparin-binding growth factor, in the intercellular interactions that are important in angiogenesis. In the blood vessel model, Midkine induced stratification of the endothelial cells and increased their proliferation and glycosaminoglycan synthesis. However, Midkine had no effect on the smooth muscle cells or endothelial cells when they were cultured separately. Increased proliferation of the endothelial cells was also attained by coculturing them with smooth muscle cells in the presence of Midkine or culturing endothelial cells with the conditioned medium of the smooth muscle cells, which had been treated with Midkine. These experiments indicate that the target of Midkine was smooth muscle cells, which secreted factor(s) acting on the endothelial cells. We identified interleukin-8 as one such factor; the synthesis of interleukin-8 by the smooth muscle cells was increased by exposure to Midkine, and anti-interleukin-8 inhibited the Midkine action. Furthermore, interleukin-8 caused stratification of the endothelial cells in the blood vessel model. These results provided evidence that Midkine is one of the factors involved in epithelial-mesenchymal interactions.

  • a heparin binding growth factor Midkine binds to a chondroitin sulfate proteoglycan pg m versican
    FEBS Journal, 2000
    Co-Authors: Kun Zou, Hisako Muramatsu, Shinya Ikematsu, Sadatoshi Sakuma, Ragaa H M Salama, Tamayuki Shinomura, Koji Kimata, Takashi Muramatsu
    Abstract:

    Midkine is a heparin-binding growth factor with survival-promoting and migration-enhancing activities. In order to understand the regulation of Midkine signaling, we isolated Midkine-binding proteoglycans from day 13 mouse embryos, when Midkine is intensely expressed. Deglycosylation followed by SDS/PAGE revealed various protein bands; one of these was identified as PG-M/versican by in gel trypsin digestion and sequencing the resulting peptides. PG-M/versican isolated from day 13 mouse embryos bound Midkine with a Kd of 1.0 nm. Pleiotrophin/heparin-binding growth-associated molecule, which has a structure related to Midkine, was also bound similarly. Digestion with chondroitinase ABC, AC-I or B abolished the binding to Midkine. Heparin as well as chondroitin sulfate D and E inhibited the binding. After chondroitinase ABC digestion, the Midkine-binding PG-M/versican released 4-sulfated, 6-sulfated, 2,6-disulfated and 4,6-disulfated unsaturated disaccharides. These results suggest that Midkine binds to a polysulfated domain in the chondroitin sulfate chain with a region of dermatan sulfate structure. This proteoglycan may modulate the Midkine activity, as binding to Midkine can enhance Midkine action by concentrating it to the cell periphery or inhibit the action by competing with the binding to a signaling receptor.

  • a receptor like protein tyrosine phosphatase ptpζ rptpβ binds a heparin binding growth factor Midkine involvement of arginine 78 of Midkine in the high affinity binding to ptpζ
    Journal of Biological Chemistry, 1999
    Co-Authors: Nobuaki Maeda, Takashi Muramatsu, Kenji Kadomatsu, Keiko Ichiharatanaka, Terutoshi Kimura, Masaharu Noda
    Abstract:

    Abstract Midkine is a 13-kDa heparin-binding growth factor with 45% sequence identity to pleiotrophin. Pleiotrophin has been demonstrated to bind to protein-tyrosine phosphatase ζ (PTPζ) with high affinity. In this study, we examined the binding of Midkine to PTPζ by solid-phase binding assay. Midkine and pleiotrophin binding to PTPζ were equally inhibited by soluble pleiotrophin and also by some specific glycosaminoglycans. For both bindings, Scatchard analysis revealed low (3.0 nm) and high (0.58 nm) affinity binding sites. These results suggested that PTPζ is a common receptor for Midkine and pleiotrophin. Midkine is structurally divided into the N- and C-terminal halves, and the latter exhibited full activity for PTPζ binding and neuronal migration induction. The C-terminal half contains two heparin-binding sites consisting of clusters of basic amino acids, Clusters I and II. A mutation at Arg78 in Cluster I resulted in loss of the high affinity binding and reduced neuronal migration-inducing activity, while mutations at Lys83 and Lys84 in Cluster II showed almost no effect on either activity. Chondroitinase ABC-treated PTPζ exhibited similar low affinity binding both to the native Midkine and Midkine mutants at Arg78. These results suggested that Arg78 in Midkine plays an essential role in high affinity binding to PTPζ by interacting with the chondroitin sulfate portion of this receptor.

  • Beneficial effect of a retinoic acid responsive gene product, Midkine, on constant light-induced retinal damage in albino mice
    Nippon Ganka Gakkai zasshi, 1995
    Co-Authors: Unoki K, Akiko Okubo, Arimura H, Fumiyuki Uehara, Muramatsu H, K. Kadomatsu, Takashi Muramatsu
    Abstract:

    We studied the protective effects of Midkine, a growth factor produced by a retinoic acid responsive gene, on constant light-induced retinal damage in albino BALB/C adult mice. Two days before exposure to constant light, Midkine was injected into the vitreous of the left eye and a phosphate buffer saline into the right eye (control eyes). After 7 days of constant light, control eyes exhibited shortening of the photoreceptor outer segments and decreased thickness of the outer nuclear layer, whereas in Midkine-treated eyes photoreceptor cells were virtually intact. Although Midkine-treated eyes also showed photoreceptor damage after longer light exposure of up to 21 days, the damage was significantly less than in control eyes. Measurement of the thickness of the outer nuclear layer showed the protective effect of intravitreous Midkine on the constant light-induced retinal damage. These findings suggest that Midkine is a potential agent for the prevention of photoreceptor degeneration.

Barry J. Dickson - One of the best experts on this subject based on the ideXlab platform.

  • comm sorts robo to control axon guidance at the drosophila midline
    Cell, 2002
    Co-Authors: Krystyna Keleman, Gerhard M Technau, Srikanth Rajagopalan, Diana Cleppien, David Teis, Karin Paiha, Lukas A Huber, Barry J. Dickson
    Abstract:

    Axon growth across the Drosophila midline requires Comm to downregulate Robo, the receptor for the midline repellent Slit. We show here that comm is required in neurons, not in midline cells as previously thought, and that it is expressed specifically and transiently in commissural neurons. Comm acts as a sorting receptor for Robo, diverting it from the synthetic to the late endocytic pathway. A conserved cytoplasmic LPSY motif is required for endosomal sorting of Comm in vitro and for Comm to downregulate Robo and promote midline crossing in vivo. Axon traffic at the CNS midline is thus controlled by the intracellular trafficking of the Robo guidance receptor, which in turn depends on the precisely regulated expression of the Comm sorting receptor.

  • Selecting a longitudinal pathway: Robo receptors specify the lateral position of axons in the Drosophila CNS.
    Cell, 2000
    Co-Authors: S. Rajagopalan, V. Vivancos, Emmanuelle Nicolas, Barry J. Dickson
    Abstract:

    On each side of the midline of the Drosophila CNS, axons are organized into a series of parallel pathways. Here we show that the midline repellent Slit, previously identified as a short-range signal that regulates midline crossing, also functions at long range to pattern these longitudinal pathways. In this long-range function, Slit signals through the receptors Robo2 and Robo3. Axons expressing neither, one, or both of these receptors project in one of three discrete lateral zones, each successively further from the midline. Loss of robo2 or robo3 function repositions axons closer to the midline, while gain of robo2 or robo3 function shifts axons further from the midline. Local cues further refine the lateral position. Together, these long- and short-range guidance cues allow growth cones to select with precision a specific longitudinal pathway.

Takashi Suzuki - One of the best experts on this subject based on the ideXlab platform.

  • flamingo a seven pass transmembrane cadherin cooperates with netrin frazzled in drosophila midline guidance
    Genes to Cells, 2015
    Co-Authors: Christina Organisti, Irina Hein, Ilona Grunwald C Kadow, Takashi Suzuki
    Abstract:

    During central nervous system development, several guidance cues and receptors, as well as cell adhesion molecules, are required for guiding axons across the midline and along the anterior–posterior axis. In Drosophila, commissural axons sense the midline attractants Netrin A and B (Net) through Frazzled (Fra) receptors. Despite their importance, lack of Net or fra affects only some commissures, suggesting that additional molecules can fulfill this function. Recently, planar cell polarity (PCP) proteins have been implicated in midline axon guidance in both vertebrate and invertebrate systems. Here, we report that the atypical cadherin and PCP molecule Flamingo/Starry night (Fmi/Stan) acts jointly with Net/Fra signaling during midline development. Additional removal of fmi strongly increases the guidance defects in Net/fra mutants. Rescue and domain deletion experiments suggest that Fmi signaling facilitates commissural pathfinding potentially by mediating axonal fasciculation in a partly homophilic manner. Altogether, our results indicate that contact-mediated cell adhesion via Fmi acts in addition to the Net/Fra guidance system during axon pathfinding across the midline, underlining the importance of PCP molecules during vertebrates and invertebrates midline development.

Mary E Fallat - One of the best experts on this subject based on the ideXlab platform.

  • thyroglossal duct and other congenital midline cervical anomalies
    Seminars in Pediatric Surgery, 2006
    Co-Authors: David S Foley, Mary E Fallat
    Abstract:

    Thyroglossal duct anomalies and dermoid cysts comprise the vast majority of congenital midline cervical masses seen in children. Unusual lesions of the midline neck include ranulae and midline cervical clefts. Workup and management is lesion-dependent, and an accurate preoperative diagnosis is essential for planning and performing an appropriate surgical procedure. This discussion presents an overview of the relevant embryology, pathophysiology, and diagnostic modalities for these congenital midline cervical anomalies. Additionally, the current principles of surgical management are described.

Corey S Goodman - One of the best experts on this subject based on the ideXlab platform.

  • slit is the midline repellent for the robo receptor in drosophila
    Cell, 1999
    Co-Authors: Thomas Kidd, Kimberly S Bland, Corey S Goodman
    Abstract:

    Previous studies suggested that Roundabout (Robo) is a repulsive guidance receptor on growth cones that binds to an unknown midline ligand. Here we present genetic evidence that Slit is the midline Robo ligand; a companion paper presents biochemical evidence that Slit binds Robo. Slit is a large extracellular matrix protein expressed by midline glia. In slit mutants, growth cones enter the midline but never leave it; they abnormally continue to express high levels of Robo while at the midline. slit and robo display dosage-sensitive genetic interactions, indicating that they function in the same pathway. slit is also required for migration of muscle precursors away from the midline. Slit appears to function as a short-range repellent controlling axon crossing of the midline and as a long-range chemorepellent controlling mesoderm migration away from the midline.

  • roundabout controls axon crossing of the cns midline and defines a novel subfamily of evolutionarily conserved guidance receptors
    Cell, 1998
    Co-Authors: Thomas Kidd, Corey S Goodman, Katja Brose, Kevin J Mitchell, Richard D Fetter, Marc Tessierlavigne, Guy Tear
    Abstract:

    The robo gene in Drosophila was identified in a large-scale mutant screen for genes that control the decision by axons to cross the CNS midline. In robo mutants, too many axons cross and recross the midline. Here we show that robo encodes an axon guidance receptor that defines a novel subfamily of immunoglobulin superfamily proteins that is highly conserved from fruit flies to mammals. For those axons that never cross the midline, Robo is expressed on their growth cones from the outset; for the majority of axons that do cross the midline, Robo is expressed at high levels on their growth cones only after they cross the midline. Transgenic rescue experiments reveal that Robo can function in a cell-autonomous fashion. Robo appears to function as the gatekeeper controlling midline crossing.