Plasmin generation dependent on α-enolase-type plasminogen receptor is required for myogenesis

Roser López-Alemany; Mònica Suelves; Pura Muñoz-Cánoves

doi:10.1160/TH03-04-0291

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 90(04): 724-733
DOI: 10.1160/TH03-04-0291

Cellular Proteolysis and Oncology

Schattauer GmbH

Plasmin generation dependent on α-enolase-type plasminogen receptor is required for myogenesis

Roser López-Alemany

¹Institut de Recerca Oncològica (IRO), Centre d’Oncología Molecular, L’Hospitalet de Llobregat, Barcelona, Spain

,

Mònica Suelves

²Centre de Regulació Genòmica (CRG), Programa de Diferenciació i Cancer, Barcelona, Spain

,

Pura Muñoz-Cánoves

²Centre de Regulació Genòmica (CRG), Programa de Diferenciació i Cancer, Barcelona, Spain

› Author Affiliations

Abstract

Summary

Plasmin is a potent extracellular protease specialized in the degradation of fibrin (fibrinolysis). Active plasmin is generated by proteolytic activation of the zymogen plasminogen (Plg) by urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). α-Enolase constitutes a receptor for plasminogen on several leukocyte cell types, serving to localize and promote plasminogen activation pericellularly. However, a role for α-enolase-type plasminogen receptor (PlgR) in myogenesis has never been demonstrated. In this study, we show that C2C12 mouse myoblasts express PlgR, being its expression greatly induced during the differentiation process. A monoclonal antibody against PIgR MAb 11G1, with cell surface-generated plasmin inhibitory abilities, was able to fully abrogate C2C12 myoblast fusion and differentiation in vitro. Moreover, both plasmin activity and PlgR expression were significantly induced in regenerating skeletal muscle in vivo, either in experimentally-injured muscle or in the dystrophic muscle of mdx mouse (an animal model of human Duchenne muscular dystrophy, DMD). The mdx muscle presents better regeneration capacities and less fibrosis than the human DMD muscle; therefore, the increase in PlgR/plasmin activity in mdx muscle suggests an important contribution of the fibrinolytic system in mdx regeneration. This study constitutes the first indication of α-enolase-type plasminogen receptor as an important component of skeletal myogenesis, by concentrating and enhancing plasmin generation on the cell surface.

Keywords

α-Enolase-type plasminogen receptor - myogenesis - muscle regeneration - mdx mice - Duchenne muscular dystrophy

Full Text

References

References
1 Irigoyen JP, Munoz-Canoves P, Montero L. et al. The plasminogen activator system: biology and regulation. Cell Mol Life Sci 1999; 56: 104-32.
2 Collen D. Lijnen HR. Basic and clinical aspects of fibrinolysis and thrombolysis. Blood 1991; 78: 3114-24.
3 Miles LA, Dahlberg CM, Plescia J. et al. Role of cell surface-lysines in plasminogen binding to cells: identification of α-enolasa as a candidate plasminogen receptor. Biochemistry 1990; 30: 1682-91.
4 Lopez-Alemany R, Correc P, Camoin L. et al. Purification of the plasmin receptor from human carcinoma cells and comparison to alpha-enolase. Thromb Res 1994; 75: 371-81.
5 Hajjar KA, Jacovina AT. Molecular cloning of a endothelial cell tissue plasminogen activator/plasminogen receptor: annexin II-related protein. Thromb Haemost 1993; 69: 989A-1601.
6 Cesarman GM, Guevara CA, Hajjar KA. An endothelial cell receptor for plasminogen/tissue plasminogen activator (t-PA). II. Annexin II-mediated enhancement of t-PA-dependent plasminogen activation. J Biol Chem 1994; 269: 21198-203.
7 Blasi F, Carmeliet P. uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol 2002; 3: 932-43.
8 Pancholi V. Multifunctional alpha-enolase: its role in diseases. Cell Mol Life Sci 2001; 58: 902-20.
9 Miles LA, Dahlberg CM, Plescia J. et al. Role of cell-surface lysines in plasminogen binding to cells: identification of α-enolase as candidate plasminogen receptor. Biochemistry 1991; 30: 1682-91.
10 Redlitz A, Fowler BJ, Plow EF. et al. The role of an enolase-related molecule in plasminogen binding to cells. Eur J Biochem 1995; 227: 407-15.
11 Miles LA, Fless GM, Scanu AM. et al. Interaction of Lp(a) with plasminogen binding sites on cells. Thromb Haemost 1995; 73: 458-65.
12 Lopez-Alemany R, Longstaff C, Hawley S. et al. Inhibition of cell surface mediated plasminogen activation by a monoclonal antibody against alpha-enolase. Am J Hematology 2003; 72: 234-42.
13 Pimorady-Esfahani A, Grounds M, McMenamin PG. Macrophages and dendritic cells in normal and regenerating murine skeletal muscle. Muscle Nerve 1997; 20: 158-66.
14 Hughes SM, Blau HM. Migration of myo-blasts across basal lamina during skeletal muscle development. Nature (London) 1990; 345: 350-3.
15 Couch CB, Strittmatter WJ. Rat myoblast fusion requires metalloendoprotease activity. Cell 1983; 32: 257-65.
16 Guerin CW, Holland PC. Synthesis and secretion of matri-degrading metalloproteases by human skeletal muscle satellite cells. Dev Dyn 1995; 202: 91-9.
17 Yagami-Hiromasa T, Sato T, Kurisaki T. et al. A metalloprotease-disintegrin participating in myoblast fusion. Nature (London) 1995; 377: 652-6.
18 Gogos JA, Thompson R, Lowry W. et al. Gene trapping in differentiating cells lines: Regulation of the lysosomal protease cathep-sin B in skeletal myoblast growth and fusion. J Cell Biol 1996; 134: 837-47.
19 Lewis MP, Tippett HL, Sinanan AC. et al. Gelatinase-B (matrix metalloproteinase-9; MMP-9) secretion is involved in the migratory phase of human and murine muscle cell cultures. J Muscle Res Cell Motil 2000; 21: 223-33.
20 Kherif S, Lafuma C, Dehaupas M. et al. Expression of matrix metalloproteinases 2 and 9 in regenerating skeletal muscle: a study in experimentally injured and mdx muscles. Dev Biol 1999; 205: 158-70.
21 El Fahime E, Torrente Y, Caron NJ. et al. In vivo migration of transplanted myoblasts requires matrix metalloproteinase activity. Exp Cell Res 2000; 258: 279-87.
22 Lijnen HR, Van Hoef B, Lupu F. et al. Function of the plasminogen/plasmin and matrix metalloproteinase systems after vascular injury in mice with targeted inactivation of fibrinolytic system genes. Artherios Thromb Vasc Biol 1998; 18: 135-45.
23 Miskin R, Easton TG, Reich E. Plasminogen activator in chick embryo muscle cells: Induction of enzyme by RSV, PMA and retinoic acid. Cell 1978; 15: 1301-12.
24 Quax PHA, Frisdal E, Pedersen N. et al. Modulation of activities and RNA level of the components of the plasminogen activation system during fusion of human myogenic satellite cells in vitro. Dev Biol 1992; 151: 166-75.
25 Barlovatz-Meimon G, Frisdal E, Hantai D. et al. Slow and fast rat skeletal muscles differ in their plasminogen activator activities. Eur J Cell Biol 1990; 52: 157-62.
26 Munoz-Canoves P, Miralles F, Baiget M. et al. Inhibition of urokinase-type plasminogen activator (uPA) abrogates myogenesis in vitro. Thromb Haemost 1997; 77: 526-34.
27 Lluis F, Roma J, Suelves M. et al. Urokinase-dependent plasminogen activation is required for efficient skeletal muscle regeneration in vivo. Blood 2001; 97: 1703-11.
28 Suelves M, Lopez-Alemany R, Lluis F. et al. Plasmin activity is required for myogenesis in vitro and skeletal muscle regeneration in vivo. Blood 2002; 99: 2835-44.
29 Cooper RN, Tajbakhsh S, Mouly V. et al. In vivo satellite cell activation via Myf5 and MyoD in regenerating mouse skeletal muscle. J Cell Sci. 1999; 112: 2895-901.
30 Longstaff C, Merton ER, Sinniger VA. A comparison of cultured cells with other promoters of tissue plasminogen activator kinetics. Fibrinolysis 1995; 9: 178-87.
31 Blau HM, Pavlath GK, Hardeman EC. et al. Plasticity of the differentiated state. Science 1985; 230: 758-66.
32 Gredinger E, Gerber AN, Tamir Y. et al. Mitogen-activated protein kinase pathway is involved in the differentiation of muscle cells. J Biol Chem 1998; 273: 10436-44.
33 Wu Z, Woodring P, Bhakta K. et al. p38 and extracellular signal-regulated kinases regulate the myogenic program at multiple steps. Mol Cel Biol 2000; 20: 3951-64.
34 Muntoni F, Mateddu A, Marchei F. et al. Muscular weakness in the mdx mouse. J Neurol Sci 1993; 120: 71-7.
35 Pastoret C, Sebille A. mdx mice show progressive weakness and muscle deterioration with age. J Neurol Sci 1995; 129: 97-105.
36 Bridges LR. The association of cardiac muscle necrosis and inflammation with the degenerative and persistent myopathy of MDX mice. J Neurol Sci 1986; 72: 147-57.
37 Wold Enolase.F.. In Boyer P. D.. ed. The Enzymes, 3 edition. pp 499-538. New York: Academic Press; 1971
38 Merkulova T, Lucas M, Jabet C. et al. Biochemical characterization of the mouse muscle-specific enolase: developmental changes in electrophoretic variants and selective binding to toher proteins. Biochem J 1997; 323: 791-800.
39 Keller A, Ott MO, Lamande N. et al. Activation of the gene encoding the glycolytic enzyme beta-enolase during early myogenesis precedes an increase expression during fetal muscle development. Mech Dev 1992; 38: 41-54.
40 Keller A, Rouzeau J-D, Farhadian F. et al. Differential expression of alpha- and beta-eno-lase genes during rat heart development and hypertrophy. Amer J Physiol-Heart Circ Phy 1995; 38: H1843-H1851.
41 Fougerousse F, Edom-Voyard F, Merkulova T. et al. The muscle-specific enolase is an early marker of human myogenesis. J Muscle Res Cell Motil. 2002; 22: 535-44.
42 Biggar WD, Klamut HJ, Demacio PC. et al. Duchenne muscular dystrophy: current knowledge, treatment, and future prospects. Clin Orthop 2002; 401: 88-106.
43 Straub V, Campbell KP. Muscular dystrophies and the dystrophin-glycoprotein complex. Curr Opin Neurol 1997; 10: 168-75.
44 Hoffman EP, Brown JRH, Kunkel LM. Dystrophin: The protein product of the duchenne muscular dystrophy locus. Cell 1987; 51: 919-28.
45 Dangain J, Vrbova G. Muscle development in mdx mutant mice. Muscle Nerve 1984; 7: 700-4.
46 Torres LFB, Duchen LW.. The mutant mdx: Inherited myopathy in the mouse. Brain 1987; 110: 269-99.
47 Carmeliet P, Collen D. Gene targeting and gene transfer studies of the biological role of the plasminogen/plasmin system. Thromb Haemost 1995; 74: 429-36.