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Cyclophilin–CD147 interactions: a new target for anti-inflammatory therapeutics

  1. V. Yurchenko1,
  2. S. Constant2,
  3. E. Eisenmesser3,
  4. M. Bukrinsky2,*

Article first published online: 16 MAR 2010

DOI: 10.1111/j.1365-2249.2010.04115.x

Issue

Clinical & Experimental Immunology

Clinical & Experimental Immunology

Volume 160, Issue 3, pages 305–317, June 2010

Additional Information

How to Cite

Yurchenko, V., Constant, S., Eisenmesser, E. and Bukrinsky, M. (2010), Cyclophilin–CD147 interactions: a new target for anti-inflammatory therapeutics. Clinical & Experimental Immunology, 160: 305–317. doi: 10.1111/j.1365-2249.2010.04115.x

Author Information

  1. 1

    Rockefeller University, New York, NY,

  2. 2

    George Washington University Medical Center, Washington, DC, and

  3. 3

    University of Colorado Denver, School of Medicine, Aurora, CO, USA

*M. Bukrinsky, GWU Medical Center, Ross Hall Suite 734, 2300 Eye Street NW, Washington, DC 20037, USA. E-mail: mtmmib@gwumc.edu

Publication History

  1. Issue published online: 7 MAY 2010
  2. Article first published online: 16 MAR 2010
  3. Accepted for publication 13 January 2010

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References

  • 1
    Fernandez EJ, Lolis E. Structure, function, and inhibition of chemokines. Annu Rev Pharmacol Toxicol 2002; 42:469–99.
  • 2
    Bukrinsky MI. Cyclophilins: unexpected messengers in intercellular communications. Trends Immunol 2002; 23:323–5.
  • 3
    Yurchenko V, Zybarth G, O'Connor M et al. Active site residues of cyclophilin A are crucial for its signaling activity via CD147. J Biol Chem 2002; 277:22959–65.
  • 4
    Arora K, Gwinn WM, Bower MA et al. Extracellular cyclophilins contribute to the regulation of inflammatory responses. J Immunol 2005; 175:517–22.
  • 5
    Gwinn WM, Damsker J, Falahati R et al. Novel approach to inhibit asthma-mediated lung inflammation using anti-CD147 intervention. J Immunol 2006; 177:4870–9.
  • 6
    Damsker J, Bukrinsky MI, Constant SL. Preferential chemotaxis of activated human CD4+ T cells by extracellular cyclophilin A. J Leuk Biol 2007; 82:613–18.
  • 7
    Sherry B, Yarlett N, Strupp A, Cerami A. Identification of cyclophilin as a proinflammatory secretory product of lipopolysaccharide-activated macrophages. Proc Natl Acad Sci USA 1992; 89:3511–15.
  • 8
    Xu Q, Leiva MC, Fischkoff SA, Handschumacher RE, Lyttle CR. Leukocyte chemotactic activity of cyclophilin. J Biol Chem 1992; 267:11968–71.
  • 9
    Iacono KT, Brown AL, Greene MI, Saouaf SJ. CD147 immunoglobulin superfamily receptor function and role in pathology. Exp Mol Pathol 2007; 83:283–95.
  • 10
    Fossum S, Mallett S, Barclay AN. The MRC OX-47 antigen is a member of the immunoglobulin superfamily with an unusual transmembrane sequence. Eur J Immunol 1991; 21:671–9.
    Direct Link:
  • 11
    Nehme CL, Cesario MM, Myles DG, Koppel DE, Bartles JR. Breaching the diffusion barrier that compartmentalizes the transmembrane glycoprotein CE9 to the posterior-tail plasma membrane domain of the rat spermatozoon. J Cell Biol 1993; 120:687–94.
  • 12
    Altruda F, Cervella P, Gaeta ML et al. Cloning of cDNA for a novel mouse membrane glycoprotein (gp42): shared identity to histocompatibility antigens, immunoglobulins and neural-cell adhesion molecules. Gene 1989; 85:445–51.
  • 13
    Kanekura T, Miyauchi T, Tashiro M, Muramatsu T. Basigin, a new member of the immunoglobulin superfamily: genes in different mammalian species, glycosylation changes in the molecule from adult organs and possible variation in the N-terminal sequences. Cell Struct Funct 1991; 16:23–30.
  • 14
    Miyauchi T, Kanekura T, Yamaoka A, Ozawa M, Miyazawa S, Muramatsu T. Basigin, a new, broadly distributed member of the immunoglobulin superfamily, has strong homology with both the immunoglobulin V domain and the beta-chain of major histocompatibility complex class II antigen. J Biochem (Tokyo) 1990; 107:316–23.
  • 15
    Seulberger H, Lottspeich F, Risau W. The inducible blood–brain barrier specific molecule HT7 is a novel immunoglobulin-like cell surface glycoprotein. EMBO J 1990; 9:2151–8.
  • 16
    Schlosshauer B, Bauch H, Frank R. Neurothelin: amino acid sequence, cell surface dynamics and actin colocalization. Eur J Cell Biol 1995; 68:159–66.
  • 17
    Seulberger H, Unger CM, Risau W. HT7, Neurothelin, Basigin, gp42 and OX-47 – many names for one developmentally regulated immuno-globulin-like surface glycoprotein on blood–brain barrier endothelium, epithelial tissue barriers and neurons. Neurosci Lett 1992; 140:93–7.
  • 18
    Fadool JM, Linser PJ. 5A11 antigen is a cell recognition molecule which is involved in neuronal–glial interactions in avian neural retina. Dev Dyn 1993; 196:252–62.
  • 19
    Biswas C. Collagenase stimulation in cocultures of human fibroblasts and human tumor cells. Cancer Lett 1984; 24:201–7.
  • 20
    Biswas C. Tumor cell stimulation of collagenase production by fibroblasts. Biochem Biophys Res Commun 1982; 109:1026–34.
  • 21
    Ellis SM, Nabeshima K, Biswas C. Monoclonal antibody preparation and purification of a tumor cell collagenase-stimulatory factor. Cancer Res 1989; 49:3385–91.
  • 22
    DeCastro R, Zhang Y, Guo H et al. Human keratinocytes express EMMPRIN, an extracellular matrix metalloproteinase inducer. J Invest Dermatol 1996; 106:1260–5.
  • 23
    Biswas C, Zhang Y, DeCastro R et al. The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res 1995; 55:434–9.
  • 24
    Kasinrerk W, Fiebiger E, Stefanova I, Baumruker T, Knapp W, Stockinger H. Human leukocyte activation antigen M6, a member of the Ig superfamily, is the species homologue of rat OX-47, mouse basigin, and chicken HT7 molecule. J Immunol 1992; 149:847–54.
  • 25
    Tang J, Zhou Hw, Jiang Jl et al. {beta}ig-h3 is involved in the HAb18G/CD147-mediated metastasis process in human hepatoma cells. Exp Biol Med 2007; 232:344–52.
  • 26
    Staffler G, Stockinger H. CD147. J Biol Regul Homeost Agents 2000; 14:327–30.
  • 27
    Nehme CL, Fayos BE, Bartles JR. Distribution of the integral plasma membrane glycoprotein CE9 (MRC OX-47) among rat tissues and its induction by diverse stimuli of metabolic activation. Biochem J 1995; 310:693–8.
  • 28
    Gabison EE, Hoang-Xuan T, Mauviel A, Menashi S. EMMPRIN/CD147, an MMP modulator in cancer, development and tissue repair. Biochimie 2005; 87:361–8.
  • 29
    Fan QW, Kadomatsu K, Uchimura K, Muramatsu T. Embigin/basigin subgroup of the immunoglobulin superfamily: different modes of expression during mouse embryogenesis and correlated expression with carbohydrate antigenic markers. Dev Growth Differ 1998; 40:277–86.
    Direct Link:
  • 30
    Heller M, Von Der OM, Kleene R, Mohajeri MH, Schachner M. The immunoglobulin-superfamily molecule basigin is a binding protein for oligomannosidic carbohydrates: an anti-idiotypic approach. J Neurochem 2003; 84:557–65.
    Direct Link:
  • 31
    Hanna SM, Kirk P, Holt OJ, Puklavec MJ, Brown MH, Barclay AN. A novel form of the membrane protein CD147 that contains an extra Ig-like domain and interacts homophilically. BMC Biochem 2003; 4:17.
  • 32
    Clark AG, Eisen MB, Smith DR et al. Evolution of genes and genomes on the Drosophila phylogeny. Nature 2007; 450:203–18.
  • 33
    Liu F, Zhou Y, Wang ZQ et al. The Schistosoma japonicum genome reveals features of host–parasite interplay. Nature 2009; 460:345–51.
  • 34
    Du PL, Zucchetti I, De SR. Immunoglobulin superfamily receptors in protochordates: before RAG time. Immunol Rev 2004; 198:233–48.
    Direct Link:
  • 35
    Igakura T, Kadomatsu K, Taguchi O et al. Roles of basigin, a member of the immunoglobulin superfamily, in behavior as to an irritating odor, lymphocyte response, and blood–brain barrier. Biochem Biophys Res Commun 1996; 224:33–6.
  • 36
    Kuno N, Kadomatsu K, Fan QW et al. Female sterility in mice lacking the basigin gene, which encodes a transmembrane glycoprotein belonging to the immunoglobulin superfamily. FEBS Lett 1998; 425:191–4.
  • 37
    Igakura T, Kadomatsu K, Kaname T et al. A null mutation in basigin, an immunoglobulin superfamily member, indicates its important roles in peri-implantation development and spermatogenesis. Dev Biol 1998; 194:152–65.
  • 38
    Toyama Y, Maekawa M, Kadomatsu K, Miyauchi T, Muramatsu T, Yuasa S. Histological characterization of defective spermatogenesis in mice lacking the basigin gene. Anat Histol Embryol 1999; 28:205–13.
    Direct Link:
  • 39
    Ochrietor JD, Moroz TM, Kadomatsu K, Muramatsu T, Linser PJ. Retinal degeneration following failed photoreceptor maturation in 5A11/basigin null mice. Exp Eye Res 2001; 72:467–77.
  • 40
    Hori K, Katayama N, Kachi S et al. Retinal dysfunction in basigin deficiency. Invest Ophthalmol Vis Sci 2000; 41:3128–33.
  • 41
    Naruhashi K, Kadomatsu K, Igakura T et al. Abnormalities of sensory and memory functions in mice lacking Bsg gene. Biochem Biophys Res Commun 1997; 236:733–7.
  • 42
    Alexander CM, Hansell EJ, Behrendtsen O et al. Expression and function of matrix metalloproteinases and their inhibitors at the maternal–embryonic boundary during mouse embryo implantation. Development 1996; 122:1723–36.
  • 43
    Nakai M, Chen L, Nowak RA. Tissue distribution of basigin and monocarboxylate transporter 1 in the adult male mouse: a study using the wild-type and basigin gene knockout mice. Anat Rec A Discov Mol Cell Evol Biol 2006; 288:527–35.
  • 44
    Philp NJ, Ochrietor JD, Rudoy C, Muramatsu T, Linser PJ. Loss of MCT1, MCT3, and MCT4 expression in the retinal pigment epithelium and neural retina of the 5A11/basigin-null mouse. Invest Ophthalmol Vis Sci 2003; 44:1305–11.
  • 45
    Daniele LL, Sauer B, Gallagher SM, Pugh EN Jr, Philp NJ. Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice. Am J Physiol Cell Physiol 2008; 295:C451–C457.
  • 46
    Ruiz S, Castro-Castro A, Bustelo XR. CD147 inhibits the nuclear factor of activated T-cells by impairing Vav1 and Rac1 downstream signaling. J Biol Chem 2008; 283:5554–66.
  • 47
    Chen X, Su J, Chang J et al. Inhibition of CD147 gene expression via RNA interference reduces tumor cell proliferation, activation, adhesion, and migration activity in the human Jurkat T-lymphoma cell line. Cancer Invest 2008; 26:689–97.
  • 48
    Koch C, Staffler G, Huttinger R et al. T cell activation-associated epitopes of CD147 in regulation of the T cell response, and their definition by antibody affinity and antigen density. Int Immunol 1999; 11:777–86.
  • 49
    Woodhead VE, Stonehouse TJ, Binks MH et al. Novel molecular mechanisms of dendritic cell-induced T cell activation. Int Immunol 2000; 12:1051–61.
  • 50
    Staffler G, Szekeres A, Schutz GJ et al. Selective inhibition of T cell activation via CD147 through novel modulation of lipid rafts. J Immunol 2003; 171:1707–14.
  • 51
    Chiampanichayakul S, Peng-in P, Khunkaewla P, Stockinger H, Kasinrerk W. CD147 contains different bioactive epitopes involving the regulation of cell adhesion and lymphocyte activation. Immunobiology 2006; 211:167–78.
  • 52
    Cho JY, Fox DA, Horejsi V et al. The functional interactions between CD98, beta1-integrins, and CD147 in the induction of U937 homotypic aggregation. Blood 2001; 98:374–82.
  • 53
    Melchior A, Denys A, Deligny A, Mazurier J, Allain F. Cyclophilin B induces integrin-mediated cell adhesion by a mechanism involving CD98-dependent activation of protein kinase C-delta and p44/42 mitogen-activated protein kinases. Exp Cell Res 2008; 314:616–28.
  • 54
    Handschumacher RE, Harding MW, Rice J, Drugge RJ, Speicher DW. Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science 1984; 226:544–7.
  • 55
    Schiene C, Fischer G. Enzymes that catalyse the restructuring of proteins. Curr Opin Struct Biol 2000; 10:40–5.
  • 56
    Colgan J, Asmal M, Neagu M et al. Cyclophilin A regulates TCR signal strength in CD4+ T cells via a proline-directed conformational switch in Itk. Immunity 2004; 21:189–201.
  • 57
    Price ER, Zydowsky LD, Jin MJ, Baker CH, McKeon FD, Walsh CT. Human cyclophilin B: a second cyclophilin gene encodes a peptidyl-prolyl isomerase with a signal sequence. Proc Natl Acad Sci USA 1991; 88:1903–7.
  • 58
    Spik G, Haendler B, Delmas O et al. A novel secreted cyclophilin-like protein (SCYLP). J Biol Chem 1991; 266:10735–8.
  • 59
    Allain F, Boutillon C, Mariller C, Spik G. Selective assay for CyPA and CyPB in human blood using highly specific anti-peptide antibodies. J Immunol Meth 1995; 178:113–20.
  • 60
    DeCeuninck F, Allain F, Caliez A, Spik G, Vanhoutte PM. High binding capacity of cyclophilin B to chondrocyte heparan sulfate proteoglycans and its release from the cell surface by matrix metalloproteinases: possible role as a proinflammatory mediator in arthritis. Arthritis Rheum 2003; 48:2197–206.
    Direct Link:
  • 61
    Jin ZG, Melaragno MG, Liao DF et al. Cyclophilin A is a secreted growth factor induced by oxidative stress. Circ Res 2000; 87:789–96.
  • 62
    Suzuki J, Jin ZG, Meoli DF, Matoba T, Berk BC. Cyclophilin A is secreted by a vesicular pathway in vascular smooth muscle cells. Circ Res 2006; 98:811–17.
  • 63
    Coppinger JA, Cagney G, Toomey S et al. Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood 2004; 103:2096–104.
  • 64
    Schlegel J, Redzic JS, Porter CC et al. Solution characterization of the extracellular region of CD147 and its interaction with its enzyme ligand cyclophilin A. J Mol Biol 2009; 391:518–35.
  • 65
    Hanoulle X, Melchior A, Sibille N et al. Structural and functional characterization of the interaction between cyclophilin B and a heparin-derived oligosaccharide. J Biol Chem 2007; 282:34148–58.
  • 66
    Renno T, Wilson A, Dunkel C et al. A role for CD147 in thymic development. J Immunol 2002; 168:4946–50.
  • 67
    Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN, Halestrap AP. CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression. EMBO J 2000; 19:3896–904.
  • 68
    Sameshima T, Nabeshima K, Toole BP et al. Correlation of emmprin expression in vascular endothelial cells with blood–brain-barrier function: a study using magnetic resonance imaging enhanced by Gd-DTPA and immunohistochemistry in brain tumors. Virchows Arch 2003; 442:577–84.
  • 69
    Schuster VL, Lu R, Kanai N et al. Cloning of the rabbit homologue of mouse ‘basigin’ and rat ‘OX-47’: kidney cell type-specific expression, and regulation in collecting duct cells. Biochim Biophys Acta 1996; 1311:13–19.
  • 70
    Muramatsu T, Miyauchi T. Basigin (CD147): a multifunctional transmembrane protein involved in reproduction, neural function, inflammation and tumor invasion. Histol Histopathol 2003; 18:981–7.
  • 71
    Berditchevski F, Chang S, Bodorova J, Hemler ME. Generation of monoclonal antibodies to integrin-associated proteins. Evidence that alpha3beta1 complexes with EMMPRIN/basigin/OX47/M6. J Biol Chem 1997; 272:29174–80.
  • 72
    Khunkaewla P, Schiller HB, Paster W et al. LFA-1-mediated leukocyte adhesion regulated by interaction of CD43 with LFA-1 and CD147. Mol Immunol 2008; 45:1703–11.
  • 73
    Pakula R, Melchior A, Denys A, Vanpouille C, Mazurier J, Allain F. Syndecan-1/CD147 association is essential for cyclophilin B-induced activation of p44/42 mitogen-activated protein kinases and promotion of cell adhesion and chemotaxis. Glycobiology 2007; 17:492–503.
  • 74
    Pushkarsky T, Yurchenko V, Laborico A, Bukrinsky M. CD147 stimulates HIV-1 infection in a signal-independent fashion. Biochem Biophys Res Commun 2007; 363:495–9.
  • 75
    Yurchenko V, O'Connor M, Dai WW et al. CD147 is a signaling receptor for cyclophilin B. Biochem Biophys Res Commun 2001; 288:786–8.
  • 76
    Boulos S, Meloni BP, Arthur PG, Majda B, Bojarski C, Knuckey NW. Evidence that intracellular cyclophilin A and cyclophilin A/CD147 receptor-mediated ERK1/2 signalling can protect neurons against in vitro oxidative and ischemic injury. Neurobiol Dis 2007; 25:54–64.
  • 77
    Yang Y, Lu N, Zhou J, Chen ZN, Zhu P. Cyclophilin A up-regulates MMP-9 expression and adhesion of monocytes/macrophages via CD147 signalling pathway in rheumatoid arthritis. Rheumatology (Oxf) 2008; 47:1299–310.
  • 78
    Wilson MC, Meredith D, Halestrap AP. Fluorescence resonance energy transfer studies on the interaction between the lactate transporter MCT1 and CD147 provide information on the topology and stoichiometry of the complex in situ. J Biol Chem 2002; 277:3666–72.
  • 79
    Gallagher SM, Castorino JJ, Philp NJ. Interaction of monocarboxylate transporter 4 with beta1-integrin and its role in cell migration. Am J Physiol Cell Physiol 2009; 296:C414–C421.
  • 80
    Tang W, Hemler ME. Caveolin-1 regulates matrix metalloproteinases-1 induction and CD147/EMMPRIN cell surface clustering. J Biol Chem 2004; 279:11112–18.
  • 81
    Jia L, Wang S, Zhou H, Cao J, Hu Y, Zhang J. Caveolin-1 up-regulates CD147 glycosylation and the invasive capability of murine hepatocarcinoma cell lines. Int J Biochem Cell Biol 2006; 38:1584–93.
  • 82
    Du ZM, Hu CF, Shao Q et al. Upregulation of caveolin-1 and CD147 expression in nasopharyngeal carcinoma enhanced tumor cell migration and correlated with poor prognosis of the patients. Int J Cancer 2009; 125:1832–41.
    Direct Link:
  • 83
    Deora AA, Gravotta D, Kreitzer G, Hu J, Bok D, Rodriguez-Boulan E. The basolateral targeting signal of CD147 (EMMPRIN) consists of a single leucine and is not recognized by retinal pigment epithelium. Mol Biol Cell 2004; 15:4148–65.
  • 84
    Marmorstein AD, Finnemann SC, Bonilha VL, Rodriguez-Boulan E. Morphogenesis of the retinal pigment epithelium: toward understanding retinal degenerative diseases. Ann NY Acad Sci 1998; 857:1–12.
    Direct Link:
  • 85
    Clamp MF, Ochrietor JD, Moroz TP, Linser PJ. Developmental analyses of 5A11/Basigin, 5A11/Basigin-2 and their putative binding partner MCT1 in the mouse eye. Exp Eye Res 2004; 78:777–89.
  • 86
    Pushkarsky T, Yurchenko V, Vanpouille C et al. Cell surface expression of CD147/EMMPRIN is regulated by cyclophilin 60. J Biol Chem 2005; 280:27866–71.
  • 87
    Ke H, Huai Q. Crystal structures of cyclophilin and its partners. Front Biosci 2004; 9:2285–96.
  • 88
    Taylor PM, Woodfield RJ, Hodgkin MN et al. Breast cancer cell-derived EMMPRIN stimulates fibroblast MMP2 release through a phospholipase A(2) and 5-lipoxygenase catalyzed pathway. Oncogene 2002; 21:5765–72.
  • 89
    Hanata K, Yamaguchi N, Yoshikawa K et al. Soluble EMMPRIN (extra-cellular matrix metalloproteinase inducer) stimulates the migration of HEp-2 human laryngeal carcinoma cells, accompanied by increased MMP-2 production in fibroblasts. Arch Histol Cytol 2007; 70:267–77.
  • 90
    Sidhu SS, Mengistab AT, Tauscher AN, LaVail J, Basbaum C. The microvesicle as a vehicle for EMMPRIN in tumor–stromal interactions. Oncogene 2004; 23:956–63.
  • 91
    Millimaggi D, Mari M, D'Ascenzo S et al. Tumor vesicle-associated CD147 modulates the angiogenic capability of endothelial cells. Neoplasia 2007; 9:349–57.
  • 92
    Egawa N, Koshikawa N, Tomari T, Nabeshima K, Isobe T, Seiki M. Membrane Type 1 matrix metalloproteinase (MT1-MMP/MMP-14) cleaves and releases a 22-kDa extracellular matrix metalloproteinase inducer (EMMPRIN) fragment from tumor cells. J Biol Chem 2006; 281:37576–85.
  • 93
    Guo H, Li R, Zucker S, Toole BP. EMMPRIN (CD147), an inducer of matrix metalloproteinase synthesis, also binds interstitial collagenase to the tumor cell surface. Cancer Res 2000; 60:888–91.
  • 94
    Haug C, Lenz C, Diaz F, Bachem MG. Oxidized low-density lipoproteins stimulate extracellular matrix metalloproteinase Inducer (EMMPRIN) release by coronary smooth muscle cells. Arterioscler Thromb Vasc Biol 2004; 24:1823–9.
  • 95
    Tang Y, Kesavan P, Nakada MT, Yan L. Tumor–stroma interaction: positive feedback regulation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN. Mol Cancer Res 2004; 2:73–80.
  • 96
    Belton RJ Jr, Chen L, Mesquita FS, Nowak RA. Basigin-2 is a cell surface receptor for soluble basigin ligand. J Biol Chem 2008; 283:17805–14.
  • 97
    Guo H, Zucker S, Gordon MK, Toole BP, Biswas C. Stimulation of matrix metalloproteinase production by recombinant extracellular matrix metalloproteinase inducer from transfected Chinese hamster ovary cells. J Biol Chem 1997; 272:24–7.
  • 98
    Sun J, Hemler ME. Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions. Cancer Res 2001; 61:2276–81.
  • 99
    Luo J, Teplyakov A, Obmolova G et al. Structure of the EMMPRIN N-terminal domain 1: dimerization via beta-strand swapping. Proteins 2009; 77:1009–14.
    Direct Link:
  • 100
    Troyanovsky S. Cadherin dimers in cell–cell adhesion. Eur J Cell Biol 2005; 84:225–33.
  • 101
    Hatherley D, Graham SC, Turner J, Harlos K, Stuart DI, Barclay AN. Paired receptor specificity explained by structures of signal regulatory proteins alone and complexed with CD47. Mol Cell 2008; 31:266–77.
  • 102
    Lim M, Martinez T, Jablons D et al. Tumor-derived EMMPRIN (extracellular matrix metalloproteinase inducer) stimulates collagenase transcription through MAPK p38. FEBS Lett 1998; 441:88–92.
  • 103
    Pushkarsky T, Zybarth G, Dubrovsky L et al. CD147 facilitates HIV-1 infection by interacting with virus-associated cyclophilin A. Proc Natl Acad Sci USA 2001; 98:6360–5.
  • 104
    Chen Z, Mi L, Xu J et al. Function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome coronavirus. J Infect Dis 2005; 191:755–60.
  • 105
    Winkler E, Hobson S, Fukumori A et al. Purification, pharmacological modulation, and biochemical characterization of interactors of endogenous human gamma-secretase. Biochemistry 2009; 48:1183–97.
  • 106
    Vetrivel KS, Zhang X, Meckler X et al. Evidence that CD147 modulation of beta-amyloid (Abeta) levels is mediated by extracellular degradation of secreted Abeta. J Biol Chem 2008; 283:19489–98.
  • 107
    Nabeshima K, Iwasaki H, Koga K, Hojo H, Suzumiya J, Kikuchi M. Emmprin (basigin/CD147): matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression. Pathol Int 2006; 56:359–67.
    Direct Link:
  • 108
    Yan L, Zucker S, Toole BP. Roles of the multifunctional glycoprotein, emmprin (basigin; CD147), in tumour progression. Thromb Haemost 2005; 93:199–204.
  • 109
    Zucker S, Hymowitz M, Rollo EE et al. Tumorigenic potential of extracellular matrix metalloproteinase inducer. Am J Pathol 2001; 158:1921–8.
  • 110
    Thorns C, Bernd HW, Hatton D, Merz H, Feller AC, Lange K. Matrix-metalloproteinases in Hodgkin lymphoma. Anticancer Res 2003; 23:1555–8.
  • 111
    Michel RB, Ochakovskaya R, Mattes MJ. Antibody localization to B-cell lymphoma xenografts in immunodeficient mice: importance of using residualizing radiolabels. Clin Cancer Res 2002; 8:2632–9.
  • 112
    Kanekura T, Chen X, Kanzaki T. Basigin (CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts. Int J Cancer 2002; 99:520–8.
    Direct Link:
  • 113
    Bordador LC, Li X, Toole B et al. Expression of emmprin by oral squamous cell carcinoma. Int J Cancer 2000; 85:347–52.
    Direct Link:
  • 114
    Davidson B, Goldberg I, Berner A, Kristensen GB, Reich R. EMMPRIN (extracellular matrix metalloproteinase inducer) is a novel marker of poor outcome in serous ovarian carcinoma. Clin Exp Metastasis 2003; 20:161–9.
  • 115
    Tsai WC, Chao YC, Lee WH, Chen A, Sheu LF, Jin JS. Increasing EMMPRIN and matriptase expression in hepatocellular carcinoma: tissue microarray analysis of immunohistochemical scores with clinicopathological parameters. Histopathology 2006; 49:388–95.
    Direct Link:
  • 116
    Zhang Q, Zhou J, Ku XM et al. Expression of CD147 as a significantly unfavorable prognostic factor in hepatocellular carcinoma. Eur J Cancer Prev 2007; 16:196–202.
  • 117
    Als AB, Dyrskjot L, Von Der MH et al. Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer. Clin Cancer Res 2007; 13:4407–14.
  • 118
    Ju XZ, Yang JM, Zhou XY, Li ZT, Wu XH. EMMPRIN expression as a prognostic factor in radiotherapy of cervical cancer. Clin Cancer Res 2008; 14:494–501.
  • 119
    Sienel W, Polzer B, Elshawi K et al. Cellular localization of EMMPRIN predicts prognosis of patients with operable lung adenocarcinoma independent from MMP-2 and MMP-9. Mod Pathol 2008; 21:1130–8.
  • 120
    Wu W, Wang R, Liu H et al. Prediction of prognosis in gallbladder carcinoma by CD147 and MMP-2 immunohistochemistry. Med Oncol 2009; 26:117–23.
  • 121
    Huet E, Gabison EE, Mourah S, Menashi S. Role of emmprin/CD147 in tissue remodeling. Connect Tissue Res 2008; 49:175–9.
  • 122
    Zavadzkas JA, Plyler RA, Bouges S et al. Cardiac-restricted overexpression of extracellular matrix metalloproteinase inducer causes myocardial remodeling and dysfunction in aging mice. Am J Physiol Heart Circ Physiol 2008; 295:H1394–H1402.
  • 123
    Huet E, Vallee B, Szul D et al. Extracellular matrix metalloproteinase inducer/CD147 promotes myofibroblast differentiation by inducing alpha-smooth muscle actin expression and collagen gel contraction: implications in tissue remodeling. FASEB J 2008; 22:1144–54.
  • 124
    Levick SP, Brower GL. Regulation of matrix metalloproteinases is at the heart of myocardial remodeling. Am J Physiol Heart Circ Physiol 2008; 295:H1375–H1376.
  • 125
    Yang H, Chen J, Yang J, Qiao S, Zhao S, Yu L. Cyclophilin A is upregulated in small cell lung cancer and activates ERK1/2 signal. Biochem Biophys Res Commun 2007; 361:763–7.
  • 126
    Li M, Zhai Q, Bharadwaj U et al. Cyclophilin A is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147. Cancer 2006; 106:2284–94.
    Direct Link:
  • 127
    Hasaneen NA, Zucker S, Cao J, Chiarelli C, Panettieri RA, Foda HD. Cyclic mechanical strain-induced proliferation and migration of human airway smooth muscle cells: role of EMMPRIN and MMPs. FASEB J 2005; 19:1507–9.
  • 128
    Foda HD, Rollo EE, Drews M et al. Ventilator-induced lung injury upregulates and activates gelatinases and EMMPRIN: attenuation by the synthetic matrix metalloproteinase inhibitor, Prinomastat (AG3340). Am J Respir Cell Mol Biol 2001; 25:717–24.
  • 129
    Damsker JM, Okwumabua I, Pushkarsky T, Arora K, Bukrinsky MI, Constant SL. Targeting the chemotactic function of CD147 reduces collagen-induced arthritis. Immunology 2009; 126:55–62.
    Direct Link:
  • 130
    Zhu P, Lu N, Shi ZG et al. CD147 overexpression on synoviocytes in rheumatoid arthritis enhances matrix metalloproteinase production and invasiveness of synoviocytes. Arthritis Res Ther 2006; 8.
  • 131
    Tomita T, Nakase T, Kaneko M et al. Expression of extracellular matrix metalloproteinase inducer and enhancement of the production of matrix metalloproteinases in rheumatoid arthritis. Arthritis Rheum 2002; 46:373–8.
    Direct Link:
  • 132
    Konttinen YT, Li TF, Mandelin J et al. Increased expression of extracellular matrix metalloproteinase inducer in rheumatoid synovium. Arthritis Rheum 2000; 43:275–80.
    Direct Link:
  • 133
    Pistol G, Matache C, Calugaru A et al. Roles of CD147 on T lymphocytes activation and MMP-9 secretion in systemic lupus erythematosus. J Cell Mol Med 2007; 11:339–48.
    Direct Link:
  • 134
    Shackel NA, McGuinness PH, Abbott CA, Gorrell MD, McCaughan GW. Insights into the pathobiology of hepatitis C virus-associated cirrhosis: analysis of intrahepatic differential gene expression. Am J Pathol 2002; 160:641–54.
  • 135
    Siwik DA, Kuster GM, Brahmbhatt JV et al. EMMPRIN mediates beta-adrenergic receptor-stimulated matrix metalloproteinase activity in cardiac myocytes. J Mol Cell Cardiol 2008; 44:210–17.
  • 136
    Yoon YW, Kwon HM, Hwang KC et al. Upstream regulation of matrix metalloproteinase by EMMPRIN; extracellular matrix metalloproteinase inducer in advanced atherosclerotic plaque. Atherosclerosis 2005; 180:37–44.
  • 137
    Spinale FG, Coker ML, Heung LJ et al. A matrix metalloproteinase induction/activation system exists in the human left ventricular myocardium and is upregulated in heart failure. Circulation 2000; 102:1944–9.
  • 138
    Choi EY, Kim D, Hong BK et al. Upregulation of extracellular matrix metalloproteinase inducer (EMMPRIN) and gelatinases in human atherosclerosis infected with Chlamydia pneumoniae: the potential role of Chlamydia pneumoniae infection in the progression of atherosclerosis. Exp Mol Med 2002; 34:391–400.
  • 139
    Waldow T, Witt W, Buzin A, Ulmer A, Matschke K. Prevention of ischemia/reperfusion-induced accumulation of matrix metalloproteinases in rat lung by preconditioning with nitric oxide. J Surg Res 2009; 152:198–208.
  • 140
    Dear JW, Leelahavanichkul A, Aponte A et al. Liver proteomics for therapeutic drug discovery: inhibition of the cyclophilin receptor CD147 attenuates sepsis-induced acute renal failure. Crit Care Med 2007; 35:2319–28.
  • 141
    Tegeder I, Schumacher A, John S et al. Elevated serum cyclophilin levels in patients with severe sepsis. J Clin Immunol 1997; 17:380–6.
  • 142
    Harigai M, Hara M, Takahashi N et al. Presence of autoantibodies to peptidyl-prolyl cis-trans isomerase (cyclosporin A-binding protein) in systemic lupus erythematosus. Clin Immunol Immunopathol 1992; 63:58–65.
  • 143
    Kratz A, Harding MW, Craft J, Kworth-Young CG, Handschumacher RE. Autoantibodies against cyclophilin in systemic lupus erythematosus and Lyme disease. Clin Exp Immunol 1992; 90:422–7.
  • 144
    Wang L, Wang CH, Jia JF et al. Contribution of cyclophilin A to the regulation of inflammatory processes in rheumatoid arthritis. J Clin Immunol 2009; in press.
  • 145
    Billich A, Winkler G, Aschauer H, Rot A, Peichl P. Presence of cyclophilin A in synovial fluids of patients with rheumatoid arthritis. J Exp Med 1997; 185:975–80.
  • 146
    Yurchenko V, Constant S, Bukrinsky M. Dealing with the family: CD147 interactions with cyclophilins. Immunology 2006; 117:301–9.
    Direct Link:
  • 147
    Catterall JB, Rowan AD, Sarsfield S, Saklatvala J, Wait R, Cawston TE. Development of a novel 2D proteomics approach for the identification of proteins secreted by primary chondrocytes after stimulation by IL-1 and oncostatin M. Rheumatology (Oxf) 2006; 45:1101–9.
  • 148
    De Ceuninck F, Allain F, Caliez A, Spik G, Vanhoutte PM. High binding capacity of cyclophilin B to chondrocyte heparan sulfate proteoglycans and its release from the cell surface by matrix metalloproteinases: possible role as a proinflammatory mediator in arthritis. Arthritis Rheum 2003; 48:2197–206.
    Direct Link:
  • 149
    Zhu P, Ding J, Zhou J, Dong WJ, Fan CM, Chen ZN. Expression of CD147 on monocytes/macrophages in rheumatoid arthritis: its potential role in monocyte accumulation and matrix metalloproteinase production. Arthritis Res Ther 2005; 7:R1023–R1033.
  • 150
    Treese C, Mittag A, Lange F et al. Characterization of fibroblasts responsible for cartilage destruction in arthritis. Cytometry A 2008; 73:351–60.
  • 151
    Jia J, Wang C, Shi Z et al. Inhibitory effect of CD147/HAb18 monoclonal antibody on cartilage erosion and synovitis in the SCID mouse model for rheumatoid arthritis. Rheumatology (Oxf) 2009; 48:721–6.
  • 152
    Seizer P, Schonberger T, Schott M et al. EMMPRIN and its ligand cyclophilin A regulate MT1-MMP, MMP-9 and M-CSF during foam cell formation. Atherosclerosis 2009.
  • 153
    Obchoei S, Wongkhan S, Wongkham C, Li M, Yao Q, Chen C. Cyclophilin A: potential functions and therapeutic target for human cancer. Med Sci Monit 2009; 15:RA221–RA232.
  • 154
    Zhou J, Zhu P, Jiang JL et al. Involvement of CD147 in overexpression of MMP-2 and MMP-9 and enhancement of invasive potential of PMA-differentiated THP-1. BMC Cell Biol 2005; 6:25.
  • 155
    Su J, Chen X, Kanekura T. A CD147-targeting siRNA inhibits the proliferation, invasiveness, and VEGF production of human malignant melanoma cells by down-regulating glycolysis. Cancer Lett 2009; 273:140–7.
  • 156
    Chen X, Lin J, Kanekura T et al. A small interfering CD147-targeting RNA inhibited the proliferation, invasiveness, and metastatic activity of malignant melanoma. Cancer Res 2006; 66:11323–30.
  • 157
    Kuang YH, Chen X, Su J et al. RNA interference targeting the CD147 induces apoptosis of multi-drug resistant cancer cells related to XIAP depletion. Cancer Lett 2009; 276:189–95.
  • 158
    Malesevic M, Kuhling J, Erdmann F et al. A cyclosporin derivative discriminates between extracellular and intracellular cyclophilins. Angew Chem Int Ed Engl 2010; 49:213–15.
  • 159
    Daum S, Schumann M, Mathea S et al. Isoform-specific inhibition of cyclophilins. Biochemistry 2009; 48:6268–77.
  • 160
    Sato T, Ota T, Watanabe M, Imada K, Nomizu M, Ito A. Identification of an active site of EMMPRIN for the augmentation of matrix metalloproteinase-1 and -3 expression in a co-culture of human uterine cervical carcinoma cells and fibroblasts. Gynecol Oncol 2009; 114:337–42.
  • 161
    Manoharan C, Wilson MC, Sessions RB, Halestrap AP. The role of charged residues in the transmembrane helices of monocarboxylate transporter 1 and its ancillary protein basigin in determining plasma membrane expression and catalytic activity. Mol Membr Biol 2006; 23:486–98.
  • 162
    Cai S, Bulus N, Fonseca-Siesser PM et al. CD98 modulates integrin beta1 function in polarized epithelial cells. J Cell Sci 2005; 118:889–99.
  • 163
    Xu D, Hemler ME. Metabolic activation-related CD147–CD98 complex. Mol Cell Proteomics 2005; 4:1061–71.
  • 164
    Curtin KD, Meinertzhagen IA, Wyman RJ. Basigin (EMMPRIN/CD147) interacts with integrin to affect cellular architecture. J Cell Sci 2005; 118:2649–60.
  • 165
    Yurchenko V, Pushkarsky T, Li JH, Dai WW, Sherry B, Bukrinsky M. Regulation of CD147 cell surface expression: involvement of the proline residue in the CD147 transmembrane domain. J Biol Chem 2005; 280:17013–19.
  • 166
    Allain F, Vanpouille C, Carpentier M, Slomianny MC, Durieux S, Spik G. Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix. Proc Natl Acad Sci USA 2002; 99:2714–19.
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