Skip to main content

Advertisement

SpringerLink
Log in

The Role of Heparanase in Diseases of the Glomeruli

  • Review
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

The glomerular basement membrane (GBM) is a kind of net that remains in a state of dynamic equilibrium. Heparan sulfate proteoglycans (HSPGs) are among its most important components. There are much data indicating the significance of these proteoglycans in protecting proteins such as albumins from penetrating to the urine, although some new data indicate that loss of proteoglycans does not always lead to proteinuria. Heparanase is an enzyme which cleaves β 1,4 d-glucuronic bonds in sugar groups of HSPGs. Thus it is supposed that heparanase may have an important role in the pathogenesis of proteinuria. Increased heparanase expression and activity in the course of many glomerular diseases was observed. The most widely documented is the significance of heparanase in the pathogenesis of diabetic nephropathy. Moreover, heparanase acts as a signaling molecule and may influence the concentrations of active growth factors in the GBM. It is being investigated whether heparanase inhibition may cause decreased proteinuria. The heparanase inhibitor PI-88 (phosphomannopentaose sulfate) was effective as an antiproteinuric drug in an experimental model of membranous nephropathy. Nevertheless, this drug is burdened by some toxicity, so further investigations should be considered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

APTT:

Active partial thromboplastin time

CD:

Cluster of differentiation

Egr, Ets, Sp:

Transcription factors

EW3D10, JM403, HS4C3, K5:

Domains of heparan sulfate proteoglycans

FGF:

Fibroblast growth factor

GBM:

Glomerular basement membrane

HSPGs:

Heparan sulfate proteoglycans

kb:

Kilobase

kDa:

Kilodaltons

pH:

Negative logarithm of hydrogen ion (H+) activity

RNA:

Ribonucleic acid

si-RNA:

Small interfering ribonucleic acid

TNF:

Tumor necrosis factor

VEGF:

Vascular endothelial growth factor

References

  • Abboud-Jarrous G, Rangini-Guetta Z, Aingorn H et al (2005) Site-directed mutagenesis, proteolytic cleavage, and activation of human proheparanase. J Biol Chem 280:13568–13575

    Article  PubMed  CAS  Google Scholar 

  • Baker PJ, Ochi RF, Schulze M et al (1989) Depletion of C6 prevents development of proteinuria in experimental membranous nephropathy in rats. Am J Pathol 135:185–194

    PubMed  CAS  Google Scholar 

  • Bame KJ (2001) Heparanases: endoglycosidases that degrade heparan sulfate proteoglycans. Glycobiology 11:91R–98R

    Article  PubMed  CAS  Google Scholar 

  • Baraz L, Haupt Y, Elkin M et al (2006) Tumor suppressor p53 regulates heparanase gene expression. Oncogene 25:3939–3947

    Article  PubMed  CAS  Google Scholar 

  • Bartlett MR, Cowden WB, Parish CR et al (1995) Differential effects of the anti-inflammatory compounds heparin, mannose-6-phosphate, and castanospermine on degradation of the vascular basement membrane by leukocytes, endothelial cells, and platelets. J Leukoc Biol 57:207–213

    PubMed  CAS  Google Scholar 

  • Battaglia C, Mayer U, Aumailley M et al (1992) Basement-membrane heparan sulfate proteoglycan binds to laminin by its heparan sulfate chains and to nidogen by sites in the protein core. Eur J Biochem 208:359–366

    Article  PubMed  CAS  Google Scholar 

  • Benezra M, Vlodavsky I, Bar-Shavit R (1992) Thrombin enhances degradation of heparan sulfate in the extracellular matrix by tumor cell heparanase. Exp Cell Res 201:208–215

    Article  PubMed  CAS  Google Scholar 

  • Ben-Zaken O, Tzaban S, Tal Y et al (2003) Cellular heparan sulfate participates in the metabolism of prions. J Biol Chem 278:40041–40049

    Article  PubMed  CAS  Google Scholar 

  • Bernfield M, Gotte M, Park P et al (1999) Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem 68:729–777

    Article  PubMed  CAS  Google Scholar 

  • Bitan M, Mohsen M, Levi E et al (1995) Structural requirements for inhibition of melanoma lung colonization by heparanase inhibiting species of heparin. Isr J Med Sci 31:106–118

    PubMed  CAS  Google Scholar 

  • Blouch K, Deen WM, Fauvel JP et al (1997) Molecular configuration and glomerular size selectivity in healthy and nephrotic humans. Am J Physiol 273:F430–F437

    PubMed  CAS  Google Scholar 

  • Bos H, Laverman GD, Henning RH et al (2003) Involvement of renal ACE activity in proteinuria-associated renal damage in untreated and treated adriamycin nephrotic rats. J Renin Angiotensin Aldosterone Syst 4:106–112

    Article  PubMed  CAS  Google Scholar 

  • Brown KJ, Hendry IA, Parish CR (1995) Acidic and basic fibroblast growth factor bind with differing affinity to the same heparan sulfate proteoglycan on BALB/c 3T3 cells: implications for potentiation of growth factor action by heparin. J Cell Biochem 58:6–14

    Article  PubMed  CAS  Google Scholar 

  • Butler GS, Apte SS, Willenbrock F et al (1999) Human tissue inhibitor of metalloproteinases 3 interacts with both the N- and C-terminal domains of gelatinases A and B. Regulation by polyanions. J Biol Chem 274:10846–10851

    Article  PubMed  CAS  Google Scholar 

  • Capila I, Linhardt RJ (2002) Heparin–protein interactions. Angew Chem Int Ed Engl 41:391–412

    Article  PubMed  Google Scholar 

  • Carey DJ (1997) Syndecans: multifunctional cell-surface co-receptors. Biochem J 327(Pt 1):1–16

    PubMed  CAS  Google Scholar 

  • Chen G, Wang D, Vikramadithyan R et al (2004) Inflammatory cytokines and fatty acids regulate endothelial cell heparanase expression. Biochemistry 43:4971–4977

    Article  PubMed  CAS  Google Scholar 

  • Cochran S, Li C, Fairweather JK et al (2003) Probing the interactions of phosphosulfomannans with angiogenic growth factors by surface plasmon resonance. J Med Chem 46:4601–4608

    Article  PubMed  CAS  Google Scholar 

  • Cohen MP, Surma ML (1981) [(35)S]sulfate incorporation into glomerular basement membrane glycosaminoglycans is decreased in experimental diabetes. J Lab Clin Med 98:715–722

    PubMed  CAS  Google Scholar 

  • Cohen I, Maly B, Simon I et al (2007) Tamoxifen induces heparanase expression in estrogen receptor-positive breast cancer. Clin Cancer Res 13:4069–4077

    Article  PubMed  CAS  Google Scholar 

  • David G (1993) Integral membrane heparan sulfate proteoglycans. FASEB J 7:1023–1030

    PubMed  CAS  Google Scholar 

  • Demir M, Iqbal O, Hoppensteadt DA et al (2001) Anticoagulant and antiprotease profiles of a novel natural heparinomimetic mannopentaose phosphate sulfate (PI-88). Clin Appl Thromb Hemost 7:131–140

    Article  PubMed  CAS  Google Scholar 

  • Dempsey LA, Plummer TB, Coombes S et al (2000a) Platelet heparanase in vascular responses to xenotransplantation. Transplant Proc 32:972

    Article  PubMed  CAS  Google Scholar 

  • Dempsey LA, Plummer TB, Coombes SL et al (2000b) Heparanase expression in invasive trophoblasts and acute vascular damage. Glycobiology 10:467–475

    Article  PubMed  CAS  Google Scholar 

  • Deshpande PV, Griffiths M (2005) Pulmonary thrombosis in steroid-sensitive nephrotic syndrome. Pediatr Nephrol 20:665–669

    Article  PubMed  Google Scholar 

  • Dredge K, Hammond E, Paris K et al (2009) The PG500 series: novel heparan sulfate mimetics as potent angiogenesis and heparanase inhibitors for cancer therapy. Invest New Drugs. doi:10.1007/s1063700992455

  • Durvasula RV, Shankland SJ (2006) Podocyte injury and targeting therapy: an update. Curr Opin Nephrol Hypertens 15:1–7

    Article  PubMed  Google Scholar 

  • Edovitsky E, Elkin M, Zcharia E et al (2004) Heparanase gene silencing, tumor invasiveness, angiogenesis, and metastasis. J Natl Cancer Inst 96:1219–1230

    Article  PubMed  CAS  Google Scholar 

  • Eickelberg O, Centrella M, Reiss M et al (2002) Betaglycan inhibits TGF-beta signaling by preventing type I-type II receptor complex formation. Glycosaminoglycan modifications alter betaglycan function. J Biol Chem 277:823–829

    Article  PubMed  CAS  Google Scholar 

  • Fairbanks MB, Mildner AM, Leone JW et al (1999) Processing of the human heparanase precursor and evidence that the active enzyme is a heterodimer. J Biol Chem 274:29587–29590

    Article  PubMed  CAS  Google Scholar 

  • Ferro V, Hammond E, Fairweather JK (2004) The development of inhibitors of heparanase, a key enzyme involved in tumour metastasis, angiogenesis and inflammation. Mini Rev Med Chem 4:693–702

    PubMed  CAS  Google Scholar 

  • Figg WD, Cooper MR, Thibault A et al (1994) Acute renal toxicity associated with suramin in the treatment of prostate cancer. Cancer 74:1612–1614

    Article  PubMed  CAS  Google Scholar 

  • Filmus J, Selleck SB (2001) Glypicans: proteoglycans with a surprise. J Clin Invest 108:497–501

    PubMed  CAS  Google Scholar 

  • Floege J, Kriz W, Schulze M et al (1995) Basic fibroblast growth factor augments podocyte injury and induces glomerulosclerosis in rats with experimental membranous nephropathy. J Clin Invest 96:2809–2819

    Article  PubMed  CAS  Google Scholar 

  • Francis DJ, Parish CR, McGarry M et al (2003) Blockade of vascular smooth muscle cell proliferation and intimal thickening after balloon injury by the sulfated oligosaccharide PI-88: phosphomannopentaose sulfate directly binds FGF-2, blocks cellular signaling, and inhibits proliferation. Circ Res 92:e70–e77

    Article  PubMed  CAS  Google Scholar 

  • Gambaro G, van der Woude FJ (2000) Glycosaminoglycans: use in treatment of diabetic nephropathy. J Am Soc Nephrol 11:359–368

    PubMed  CAS  Google Scholar 

  • Gilat D, Hershkoviz R, Goldkorn I et al (1995) Molecular behavior adapts to context: heparanase functions as an extracellular matrix-degrading enzyme or as a T cell adhesion molecule, depending on the local pH. J Exp Med 181:1929–1934

    Article  PubMed  CAS  Google Scholar 

  • Gingis-Velitski S, Zetser A, Kaplan V et al (2004) Heparanase uptake is mediated by cell membrane heparan sulfate proteoglycans. J Biol Chem 279:44084–44092

    Article  PubMed  CAS  Google Scholar 

  • Goldshmidt O, Zcharia E, Aingorn H et al (2001) Expression pattern and secretion of human and chicken heparanase are determined by their signal peptide sequence. J Biol Chem 276:29178–29187

    Article  PubMed  CAS  Google Scholar 

  • Goldshmidt O, Zcharia E, Abramovitch R et al (2002) Cell surface expression and secretion of heparanase markedly promote tumor angiogenesis and metastasis. Proc Natl Acad Sci USA 99:10031–10036

    Article  PubMed  CAS  Google Scholar 

  • Goldshmidt O, Zcharia E, Cohen M et al (2003) Heparanase mediates cell adhesion independent of its enzymatic activity. FASEB J 17:1015–1025

    Article  PubMed  CAS  Google Scholar 

  • Goshen R, Hochberg AA, Korner G et al (1996) Purification and characterization of placental heparanase and its expression by cultured cytotrophoblasts. Mol Hum Reprod 2:679–684

    Article  PubMed  CAS  Google Scholar 

  • Grant DS, Leblond CP, Kleinman HK et al (1989) The incubation of laminin, collagen IV, and heparan sulfate proteoglycan at 35 degrees C yields basement membrane-like structures. J Cell Biol 108:1567–1574

    Article  PubMed  CAS  Google Scholar 

  • Groffen AJ, Ruegg MA, Dijkman H et al (1998) Agrin is a major heparan sulfate proteoglycan in the human glomerular basement membrane. J Histochem Cytochem 46:19–27

    PubMed  CAS  Google Scholar 

  • Halfter W, Dong S, Schurer B et al (1998) Collagen XVIII is a basement membrane heparan sulfate proteoglycan. J Biol Chem 273:25404–25412

    Article  PubMed  CAS  Google Scholar 

  • Hayashi K, Madri JA, Yurchenco PD (1992) Endothelial cells interact with the core protein of basement membrane perlecan through beta 1 and beta 3 integrins: an adhesion modulated by glycosaminoglycan. J Cell Biol 119:945–959

    Article  PubMed  CAS  Google Scholar 

  • Hayman EG, Oldberg A, Martin GR et al (1982) Codistribution of heparan sulfate proteoglycan, laminin, and fibronectin in the extracellular matrix of normal rat kidney cells and their coordinate absence in transformed cells. J Cell Biol 94:28–35

    Article  PubMed  CAS  Google Scholar 

  • He X, Brenchley PE, Jayson GC et al (2004) Hypoxia increases heparanase-dependent tumor cell invasion, which can be inhibited by antiheparanase antibodies. Cancer Res 64:3928–3933

    Article  PubMed  CAS  Google Scholar 

  • Hershkoviz R, Mor F, Miao HQ et al (1995) Differential effects of polysulfated polysaccharide on experimental encephalomyelitis, proliferation of autoimmune T cells, and inhibition of heparanase activity. J Autoimmun 8:741–750

    Article  PubMed  CAS  Google Scholar 

  • Hilgard P, Stockert R (2000) Heparan sulfate proteoglycans initiate dengue virus infection of hepatocytes. Hepatology 32:1069–1077

    Article  PubMed  CAS  Google Scholar 

  • Holt RC, Webb NJ, Ralph S et al (2005) Heparanase activity is dysregulated in children with steroid-sensitive nephrotic syndrome. Kidney Int 67:122–129

    Article  PubMed  CAS  Google Scholar 

  • Hoogewerf AJ, Leone JW, Reardon IM et al (1995) CXC chemokines connective tissue activating peptide-III and neutrophil activating peptide-2 are heparin/heparan sulfate-degrading enzymes. J Biol Chem 270:3268–3277

    Article  PubMed  CAS  Google Scholar 

  • Hulett MD, Freeman C, Hamdorf BJ et al (1999) Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis. Nat Med 5:803–809

    Article  PubMed  CAS  Google Scholar 

  • Ihrcke NS, Parker W, Reissner KJ et al (1998) Regulation of platelet heparanase during inflammation: role of pH and proteinases. J Cell Physiol 175:255–267

    Article  PubMed  CAS  Google Scholar 

  • Ilan N, Elkin M, Vlodavsky I (2006) Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis. Int J Biochem Cell Biol 38:2018–2039

    Article  PubMed  CAS  Google Scholar 

  • Iozzo RV, Cohen IR, Grassel S et al (1994) The biology of perlecan: the multifaceted heparan sulphate proteoglycan of basement membranes and pericellular matrices. Biochem J 302(Pt 3):625–639

    PubMed  CAS  Google Scholar 

  • Irimura T, Nakajima M, Nicolson GL (1986) Chemically modified heparins as inhibitors of heparan sulfate specific endo-beta-glucuronidase (heparanase) of metastatic melanoma cells. Biochemistry 25:5322–5328

    Article  PubMed  CAS  Google Scholar 

  • Jackson RL, Busch SJ, Cardin AD (1991) Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes. Physiol Rev 71:481–539

    PubMed  CAS  Google Scholar 

  • Jiang P, Kumar A, Parrillo JE et al (2002) Cloning and characterization of the human heparanase-1 (HPR1) gene promoter: role of GA-binding protein and Sp1 in regulating HPR1 basal promoter activity. J Biol Chem 277:8989–8998

    Article  PubMed  CAS  Google Scholar 

  • Jun Z, Hill PA, Lan HY et al (1997) CD44 and hyaluronan expression in the development of experimental crescentic glomerulonephritis. Clin Exp Immunol 108:69–77

    Article  PubMed  CAS  Google Scholar 

  • Kanwar YS, Linker A, Farquhar MG (1980) Increased permeability of the glomerular basement membrane to ferritin after removal of glycosaminoglycans (heparan sulfate) by enzyme digestion. J Cell Biol 86:688–693

    Article  PubMed  CAS  Google Scholar 

  • Kashihara N, Watanabe Y, Makino H et al (1992) Selective decreased de novo synthesis of glomerular proteoglycans under the influence of reactive oxygen species. Proc Natl Acad Sci USA 89:6309–6313

    Article  PubMed  CAS  Google Scholar 

  • Katz A, Van-Dijk DJ, Aingorn H et al (2002) Involvement of human heparanase in the pathogenesis of diabetic nephropathy. Isr Med Assoc J 4:996–1002

    PubMed  CAS  Google Scholar 

  • Khong TF, Fraser S, Katerelos M et al (2000) Inhibition of heparin-binding epidermal growth factor-like growth factor increases albuminuria in puromycin aminonucleoside nephrosis. Kidney Int 58:1098–1107

    Article  PubMed  CAS  Google Scholar 

  • Koistinaho J (1990) Suramin-induced changes in sympathetic neurons: correlation between catecholamine fluorescence, tyrosine hydroxylase immunoreactivity and accumulation of pigment bodies. Neurosci Lett 112:19–24

    Article  PubMed  CAS  Google Scholar 

  • Kramer A, van den Hoven M, Rops A et al (2006) Induction of glomerular heparanase expression in rats with adriamycin nephropathy is regulated by reactive oxygen species and the renin-angiotensin system. J Am Soc Nephrol 17:2513–2520

    Article  PubMed  CAS  Google Scholar 

  • Lee E, Pavy M, Young N et al (2006) Antiviral effect of the heparan sulfate mimetic, PI-88, against dengue and encephalitic flaviviruses. Antiviral Res 69:31–38

    Article  PubMed  CAS  Google Scholar 

  • Levidiotis V, Kanellis J, Ierino FL et al (2001) Increased expression of heparanase in puromycin aminonucleoside nephrosis. Kidney Int 60:1287–1296

    Article  PubMed  CAS  Google Scholar 

  • Levidiotis V, Freeman C, Punler M et al (2004a) A synthetic heparanase inhibitor reduces proteinuria in passive Heymann nephritis. J Am Soc Nephrol 15:2882–2892

    Article  PubMed  CAS  Google Scholar 

  • Levidiotis V, Freeman C, Tikellis C et al (2004b) Heparanase is involved in the pathogenesis of proteinuria as a result of glomerulonephritis. J Am Soc Nephrol 15:68–78

    Article  PubMed  CAS  Google Scholar 

  • Levidiotis V, Freeman C, Tikellis C et al (2005) Heparanase inhibition reduces proteinuria in a model of accelerated anti-glomerular basement membrane antibody disease. Nephrology 10:167–173

    Article  PubMed  CAS  Google Scholar 

  • Lewis EJ, Xu X (2008) Abnormal glomerular permeability characteristics in diabetic nephropathy: implications for the therapeutic use of low-molecular weight heparin. Diabetes Care 31(Suppl 2):S202–S207

    Article  PubMed  CAS  Google Scholar 

  • Lewis KD, Robinson WA, Millward MJ et al (2008) A phase II study of the heparanase inhibitor PI-88 in patients with advanced melanoma. Invest New Drugs 26:89–94

    Article  PubMed  CAS  Google Scholar 

  • Li JP, Galvis ML, Gong F et al (2005) In vivo fragmentation of heparan sulfate by heparanase overexpression renders mice resistant to amyloid protein A amyloidosis. Proc Natl Acad Sci USA 102:6473–6477

    Article  PubMed  CAS  Google Scholar 

  • Lider O, Cahalon L, Gilat D et al (1995) A disaccharide that inhibits tumor necrosis factor alpha is formed from the extracellular matrix by the enzyme heparanase. Proc Natl Acad Sci USA 92:5037–5041

    Article  PubMed  CAS  Google Scholar 

  • Luo J, Kato M, Wang H et al (2001) Heparan sulfate and chondroitin sulfate proteoglycans inhibit E-selectin binding to endothelial cells. J Cell Biochem 80:522–531

    Article  PubMed  CAS  Google Scholar 

  • Marjomaki V, Salminen A (1986) Morphological and enzymatic heterogeneity of suramin-induced lysosomal storage disease in some tissues of mice and rats. Exp Mol Pathol 45:76–83

    Article  PubMed  CAS  Google Scholar 

  • Matzner Y, Bar-Ner M, Yahalom J et al (1985) Degradation of heparan sulfate in the subendothelial extracellular matrix by a readily released heparanase from human neutrophils. Possible role in invasion through basement membranes. J Clin Invest 76:1306–1313

    Article  PubMed  CAS  Google Scholar 

  • Matzner Y, Vlodavsky I, Bar-Ner M et al (1992) Subcellular localization of heparanase in human neutrophils. J Leukoc Biol 51:519–524

    PubMed  CAS  Google Scholar 

  • Maxhimer JB, Somenek M, Rao G et al (2005) Heparanase-1 gene expression and regulation by high glucose in renal epithelial cells: a potential role in the pathogenesis of proteinuria in diabetic patients. Diabetes 54:2172–2178

    Article  PubMed  CAS  Google Scholar 

  • McKenzie E, Young K, Hircock M et al (2003) Biochemical characterization of the active heterodimer form of human heparanase (Hpa1) protein expressed in insect cells. Biochem J 373:423–435

    Article  PubMed  CAS  Google Scholar 

  • McNally LM, Jeena PM, Gajee K et al (2007) Effect of age, polymicrobial disease, and maternal HIV status on treatment response and cause of severe pneumonia in South African children: a prospective descriptive study. Lancet 369:1440–1451

    Article  PubMed  CAS  Google Scholar 

  • Mertens G, Cassiman JJ, Van den Berghe H et al (1992) Cell surface heparan sulfate proteoglycans from human vascular endothelial cells. Core protein characterization and antithrombin III binding properties. J Biol Chem 267:20435–20443

    PubMed  CAS  Google Scholar 

  • Mishima T, Murata J, Toyoshima M et al (1998) Inhibition of tumor invasion and metastasis by calcium spirulan (Ca-SP), a novel sulfated polysaccharide derived from a blue-green alga, Spirulina platensis. Clin Exp Metastasis 16:541–550

    Article  PubMed  CAS  Google Scholar 

  • Mollinedo F, Nakajima M, Llorens A et al (1997) Major co-localization of the extracellular-matrix degradative enzymes heparanase and gelatinase in tertiary granules of human neutrophils. Biochem J 327(Pt 3):917–923

    PubMed  CAS  Google Scholar 

  • Moseley R, Waddington R, Evans P et al (1995) The chemical modification of glycosaminoglycan structure by oxygen-derived species in vitro. Biochim Biophys Acta 1244:245–252

    PubMed  Google Scholar 

  • Myler HA, Lipke EA, Rice EE et al (2006) Novel heparanase-inhibiting antibody reduces neointima formation. J Biochem 139:339–345

    Article  PubMed  CAS  Google Scholar 

  • Nadav L, Eldor A, Yacoby-Zeevi O et al (2002) Activation, processing and trafficking of extracellular heparanase by primary human fibroblasts. J Cell Sci 115:2179–2187

    PubMed  CAS  Google Scholar 

  • Naggi A, Casu B, Perez M et al (2005) Modulation of the heparanase-inhibiting activity of heparin through selective desulfation, graded N-acetylation, and glycol splitting. J Biol Chem 280:12103–12113

    Article  PubMed  CAS  Google Scholar 

  • Nakajima M, Irimura T, Di Ferrante N et al (1984) Metastatic melanoma cell heparanase. Characterization of heparan sulfate degradation fragments produced by B16 melanoma endoglucuronidase. J Biol Chem 259:2283–2290

    PubMed  CAS  Google Scholar 

  • Nakajima M, DeChavigny A, Johnson CE et al (1991) Suramin. A potent inhibitor of melanoma heparanase and invasion. J Biol Chem 266:9661–9666

    PubMed  CAS  Google Scholar 

  • Naparstek Y, Cohen IR, Fuks Z et al (1984) Activated T lymphocytes produce a matrix-degrading heparan sulphate endoglycosidase. Nature 310:241–244

    Article  PubMed  CAS  Google Scholar 

  • Noonan DM, Hassell JR (1993) Perlecan, the large low-density proteoglycan of basement membranes: structure and variant forms. Kidney Int 43:53–60

    Article  PubMed  CAS  Google Scholar 

  • Okada Y, Yamada S, Toyoshima M et al (2002) Structural recognition by recombinant human heparanase that plays critical roles in tumor metastasis. Hierarchical sulfate groups with different effects and the essential target disulfated trisaccharide sequence. J Biol Chem 277:42488–42495

    Article  PubMed  CAS  Google Scholar 

  • Ostendorf T, Kunter U, Eitner F et al (1999) VEGF(165) mediates glomerular endothelial repair. J Clin Invest 104:913–923

    Article  PubMed  CAS  Google Scholar 

  • Ostrovsky O, Korostishevsky M, Shafat I et al (2009) Inverse correlation between HPSE gene single nucleotide polymorphisms and heparanase expression: possibility of multiple levels of heparanase regulation. J Leukoc Biol 86:445–455

    Article  PubMed  CAS  Google Scholar 

  • Panasyuk A, Frati E, Ribault D et al (1994) Effect of reactive oxygen species on the biosynthesis and structure of newly synthesized proteoglycans. Free Radic Biol Med 16:157–167

    Article  PubMed  CAS  Google Scholar 

  • Parish CR, Freeman C, Brown KJ et al (1999) Identification of sulfated oligosaccharide-based inhibitors of tumor growth and metastasis using novel in vitro assays for angiogenesis and heparanase activity. Cancer Res 59:3433–3441

    PubMed  CAS  Google Scholar 

  • Parish CR, Freeman C, Hulett MD (2001) Heparanase: a key enzyme involved in cell invasion. Biochim Biophys Acta 1471:M99–M108

    PubMed  CAS  Google Scholar 

  • Patel M, Yanagishita M, Roderiquez G et al (1993) Cell-surface heparan sulfate proteoglycan mediates HIV-1 infection of T-cell lines. AIDS Res Hum Retroviruses 9:167–174

    Article  PubMed  CAS  Google Scholar 

  • Raats CJ, Bakker MA, Hoch W et al (1998) Differential expression of agrin in renal basement membranes as revealed by domain-specific antibodies. J Biol Chem 273:17832–17838

    Article  PubMed  CAS  Google Scholar 

  • Raats CJ, Van Den Born J, Berden JH (2000) Glomerular heparan sulfate alterations: mechanisms and relevance for proteinuria. Kidney Int 57:385–400

    Article  PubMed  CAS  Google Scholar 

  • Rees S, Constantopoulos G, Barranger JA et al (1982) Organomegaly and histopathology in an animal model of mucopolysaccharidosis induced by suramin. Naunyn Schmiedebergs Arch Pharmacol 319:262–270

    Article  PubMed  CAS  Google Scholar 

  • Rops AL, van der Vlag J, Lensen JF et al (2004) Heparan sulfate proteoglycans in glomerular inflammation. Kidney Int 65:768–785

    Article  PubMed  CAS  Google Scholar 

  • Rops AL, van den Hoven MJ, Bakker MA et al (2007) Expression of glomerular heparan sulphate domains in murine and human lupus nephritis. Nephrol Dial Transplant 22:1891–1902

    Article  PubMed  CAS  Google Scholar 

  • Rosenthal MA, Rischin D, McArthur G et al (2002) Treatment with the novel anti-angiogenic agent PI-88 is associated with immune-mediated thrombocytopenia. Ann Oncol 13:770–776

    Article  PubMed  CAS  Google Scholar 

  • Rosenzweig LJ, Kanwar YS (1982) Removal of sulfated (heparan sulfate) or nonsulfated (hyaluronic acid) glycosaminoglycans results in increased permeability of the glomerular basement membrane to 125I-bovine serum albumin. Lab Invest 47:177–184

    PubMed  CAS  Google Scholar 

  • Sasaki N, Higashi N, Taka T et al (2004) Cell surface localization of heparanase on macrophages regulates degradation of extracellular matrix heparan sulfate. J Immunol 172:3830–3835

    PubMed  CAS  Google Scholar 

  • Scholey JW, Miller PL, Rennke HG et al (1989) Effect of converting enzyme inhibition on the course of adriamycin-induced nephropathy. Kidney Int 36:816–822

    Article  PubMed  CAS  Google Scholar 

  • Sewell RF, Brenchley PE, Mallick NP et al (1989) Human mononuclear cells contain an endoglycosidase specific for heparan sulphate glycosaminoglycan demonstrable with the use of a specific solid-phase metabolically radiolabelled substrate. Biochem J 264:777–783

    PubMed  CAS  Google Scholar 

  • Shafat I, Vlodavsky I, Ilan N (2006) Characterization of mechanisms involved in secretion of active heparanase. J Biol Chem 281:23804–23811

    Article  PubMed  CAS  Google Scholar 

  • Shimomura H, Spiro RG (1987) Studies on macromolecular components of human glomerular basement membrane and alterations in diabetes. Decreased levels of heparan sulfate proteoglycan and laminin. Diabetes 36:374–381

    Article  PubMed  CAS  Google Scholar 

  • Shukla D, Liu J, Blaiklock P et al (1999) A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Cell 99:13–22

    Article  PubMed  CAS  Google Scholar 

  • Summerford C, Bartlett JS, Samulski RJ (1999) AlphaVbeta5 integrin: a co-receptor for adeno-associated virus type 2 infection. Nat Med 5:78–82

    Article  PubMed  CAS  Google Scholar 

  • Suzuki D, Yagame M, Kim Y et al (2002) Renal in situ hybridization studies of extracellular matrix related molecules in type 1 diabetes mellitus. Nephron 92:564–572

    Article  PubMed  CAS  Google Scholar 

  • Teich SA, Handwerger S, Mathur-Wagh U et al (1986) Toxic keratopathy associated with suramin therapy. N Engl J Med 314:1455–1456

    PubMed  CAS  Google Scholar 

  • van den Born J, van den Heuvel LP, Bakker MA et al (1992) A monoclonal antibody against GBM heparan sulfate induces an acute selective proteinuria in rats. Kidney Int 41:115–123

    Article  PubMed  Google Scholar 

  • van den Born J, van den Heuvel LP, Bakker MA et al (1993) Distribution of GBM heparan sulfate proteoglycan core protein and side chains in human glomerular diseases. Kidney Int 43:454–463

    Article  PubMed  Google Scholar 

  • van den Born J, Pisa B, Bakker MA et al (2006) No change in glomerular heparan sulfate structure in early human and experimental diabetic nephropathy. J Biol Chem 281:29606–29613

    Article  PubMed  CAS  Google Scholar 

  • van den Hoven MJ, Rops AL, Bakker MA (2006) Increased expression of heparanase in overt diabetic nephropathy. Kidney Int 70:2100–2108

    PubMed  Google Scholar 

  • van den Hoven MJ, Rops AL, Vlodavsky I et al (2007) Heparanase in glomerular diseases. Kidney Int 72:543–548

    Article  PubMed  CAS  Google Scholar 

  • van den Hoven MJ, Wijnhoven TJ, Li JP et al (2008) Reduction of anionic sites in the glomerular basement membrane by heparanase does not lead to proteinuria. Kidney Int 73:278–287

    Article  PubMed  CAS  Google Scholar 

  • van den Hoven MJ, Waanders F, Rops AL et al (2009) Regulation of glomerular heparanase expression by aldosterone, angiotensin II and reactive oxygen species. Nephrol Dial Transplant 24:2637–2645

    Article  PubMed  CAS  Google Scholar 

  • van Timmeren MM, Bakker SJ, Vaidya VS et al (2006) Tubular kidney injury molecule-1 in protein-overload nephropathy. Am J Physiol Renal Physiol 291:F456–F464

    Article  PubMed  CAS  Google Scholar 

  • Vernier RL, Steffes MW, Sisson-Ross S et al (1992) Heparan sulfate proteoglycan in the glomerular basement membrane in type 1 diabetes mellitus. Kidney Int 41:1070–1080

    Article  PubMed  CAS  Google Scholar 

  • Vlodavsky I, Friedmann Y (2001) Molecular properties and involvement of heparanase in cancer metastasis and angiogenesis. J Clin Invest 108:341–347

    PubMed  CAS  Google Scholar 

  • Vlodavsky I, Korner G, Ishai-Michaeli R et al (1990) Extracellular matrix-resident growth factors and enzymes: possible involvement in tumor metastasis and angiogenesis. Cancer Metastasis Rev 9:203–226

    Article  PubMed  CAS  Google Scholar 

  • Vlodavsky I, Eldor A, Haimovitz-Friedman A et al (1992) Expression of heparanase by platelets and circulating cells of the immune system: possible involvement in diapedesis and extravasation. Invasion Metastasis 12:112–127

    PubMed  CAS  Google Scholar 

  • Vlodavsky I, Friedmann Y, Elkin M et al (1999) Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis. Nat Med 5:793–802

    Article  PubMed  CAS  Google Scholar 

  • Vreys V, Delande N, Zhang Z et al (2005) Cellular uptake of mammalian heparanase precursor involves low density lipoprotein receptor-related proteins, mannose 6-phosphate receptors, and heparan sulfate proteoglycans. J Biol Chem 280:33141–33148

    Article  PubMed  CAS  Google Scholar 

  • Watanabe H, Hattori S, Katsuda S et al (1990) Human neutrophil elastase: degradation of basement membrane components and immunolocalization in the tissue. J Biochem 108:753–759

    PubMed  CAS  Google Scholar 

  • Watanabe N, Kawashima H, Li YF et al (1999) Identification and characterization of ligands for L-selectin in the kidney. III. Characterization of L-selectin reactive heparan sulfate proteoglycans. J Biochem 125:826–831

    PubMed  CAS  Google Scholar 

  • Wijnhoven TJ, Lensen JF, Wismans RG et al (2007) In vivo degradation of heparan sulfates in the glomerular basement membrane does not result in proteinuria. J Am Soc Nephrol 18:823–832

    Article  PubMed  CAS  Google Scholar 

  • Wijnhoven TJ, van den Hoven MJ, Ding H et al (2008) Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy. Diabetologia 51:372–382

    Article  PubMed  CAS  Google Scholar 

  • Witt DP, Lander AD (1994) Differential binding of chemokines to glycosaminoglycan subpopulations. Curr Biol 4:394–400

    Article  PubMed  CAS  Google Scholar 

  • Wu SH, Yang YC, Wang ZM (1990) Role of oxygen radicals in adriamycin-induced nephrosis. Chin Med J (Engl) 103:283–289

    CAS  Google Scholar 

  • Xu X, Ding J, Rao G et al (2007) Estradiol induces heparanase-1 expression and heparan sulphate proteoglycan degradation in human endometrium. Hum Reprod 22:927–937

    Article  PubMed  CAS  Google Scholar 

  • Zcharia E, Metzger S, Chajek-Shaul T et al (2004) Transgenic expression of mammalian heparanase uncovers physiological functions of heparan sulfate in tissue morphogenesis, vascularization, and feeding behavior. FASEB J 18:252–263

    Article  PubMed  CAS  Google Scholar 

  • Zetser A, Levy-Adam F, Kaplan V et al (2004) Processing and activation of latent heparanase occurs in lysosomes. J Cell Sci 117:2249–2258

    Article  PubMed  CAS  Google Scholar 

  • Zhao H, Liu H, Chen Y et al (2006) Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting basic fibroblast growth factor, combats tumor angiogenesis and metastasis. Cancer Res 66:8779–8787

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nephrology and Transplantation Medicine, Wrocław Medical University, Traugutta 57/59, 50-417, Wrocław, Poland

    Maciej Szymczak, Jakub Kuźniar & Marian Klinger

Authors
  1. Maciej Szymczak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jakub Kuźniar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marian Klinger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marian Klinger.

About this article

Cite this article

Szymczak, M., Kuźniar, J. & Klinger, M. The Role of Heparanase in Diseases of the Glomeruli. Arch. Immunol. Ther. Exp. 58, 45–56 (2010). https://doi.org/10.1007/s00005-009-0061-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00005-009-0061-6

Keywords

Search

Navigation