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High concentration but low biological activity of hepatocyte growth factor in patients with chronic renal failure

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DOI: 10.4236/abb.2012.324068    3,764 Downloads   6,310 Views   Citations

ABSTRACT

Hepatocyte growth factor (HGF) is a renotropic, antifibrotic and regenerative factor with cytoprotective effects that is produced by mesenchymal cells and shows high affinity to components of extra cellular matrix, such as heparan sulphate proteoglycan (HS-PG), in healthy. Patients with chronic renal failure (CRF) suffer from a chronic inflammatory disorder. In order to assess the underlying mechanisms for development of CRF we aimed to assess the amounts and affinity of HGF in this patient group. Elisa, western blot and surface plasmon resonance (SPR) were used to study HGF in blood samples, as well as in isolated neutrophils, in CRF patients compared to healthy controls. Patients with CRF showed higher HGF levels in serum (P < 0.0001), but decreased affinity to HSPG (P < 0.0001), compared to healthy controls. Addition of protease inhibitors decreased the difference between patients with CRF compared to healthy individuals. HGF with potent regenerative function during injury lacks affinity to HSPG in patients with CRF that may depend on production of proteases from activated immune cells. This information might be used to highlight underlying mechanisms for chronicity and leading to new strategies for treatment of chronic injuries.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Lönn, J. , Shahzad, F. , Uhlin, F. , Bengtsson, T. , Almroth, G. and Nayeri, F. (2012) High concentration but low biological activity of hepatocyte growth factor in patients with chronic renal failure. Advances in Bioscience and Biotechnology, 3, 516-523. doi: 10.4236/abb.2012.324068.

References

[1] Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453:314-21.
[2] Mizuno S, Matsumoto K, Nakamura T. HGF as a renotrophic and anti-fibrotic regulator in chronic renal disease. Front Biosci. 2008;13:7072-86.
[3] Matsumoto K, Nakamura T. Hepatocyte growth factor: renotropic role and potential therapeutics for renal diseases. Kidney Int. 2001;59:2023-38.
[4] Iekushi K, Taniyama Y, Azuma J, Sanada F, Kusunoki H, Yokoi T, et al. Hepatocyte growth factor attenuates renal fibrosis through TGF-β1 suppression by apoptosis of myofibroblasts. J Hypertens. 2010;28:2454-61.
[5] Nakamura T, Mizuno S. The discovery of hepatocyte growth factor (HGF) and its significance for cell biology, life sciences and clinical medicine. Proc Jpn Acad Ser B Phys Biol Sci. 2010;86:588-610.
[6] Yo Y, Morishita R, Nakamura S, Tomita N, Yamamoto K, Moriguchi A, et al. Potential role of hepatocyte growth factor in the maintenance of renal structure: anti-apoptotic action of HGF on epithelial cells. Kidney Int. 1998;54:1128-38.
[7] Nagaike M, Hirao S, Tajima H, Noji S, Taniguchi S, Matsumoto K, et al. Renotropic functions of hepatocyte growth factor in renal regeneration after unilateral nephrectomy. J Biol Chem. 1991;266:22781-4.
[8] Igawa T, Matsumoto K, Kanda S, Saito Y, Nakamura T. Hepatocyte growth factor may function as a renotropic factor for regeneration in rats with acute renal injury. Am J Physiol. 1993;265:F61-9.
[9] Matsumoto K, Nakamura T. Hepatocyte growth factor (HGF) as a tissue organizer for organogenesis and regeneration. Biochem Biophys Res Commun. 1997;239:639-44.
[10] Naka D, Ishii T, Yoshiyama Y, Miyazawa K, Hara H, Hishida T, et al. Activation of hepatocyte growth factor by proteolytic conversion of a single chain form to a heterodimer. J Biol Chem. 1992;267:20114-9.
[11] Grenier A, Chollet-Martin S, Crestani B, Delarche C, El Benna J, Boutten A, et al. Presence of a mobilizable intracellular pool of hepatocyte growth factor in human polymorphonuclear neutrophils. Blood. 2002;99:2997-3004.
[12] Luerman GC, Uriarte SM, Rane MJ, McLeish KR. Application of proteomics to neutrophil biology. J Proteomics. 2010;73:552-61.
[13] Cowburn AS, Condliffe AM, Farahi N, Summers C, Chilvers ER. Advances in neutrophil biology: clinical implications. Chest. 2008;134:606-12.
[14] Matsushima A, Ogura H, Koh T, Fujita K, Yoshiya K, Sumi Y, et al. Hepatocyte growth factor in polymorphonuclear leukocytes is increased in patients with systemic inflammatory response syndrome. J Trauma. 2004;56:259-64.
[15] Costa E, Rocha S, Rocha-Pereira P, Nascimento H, Castro E, Miranda V, et al. Neutrophil activation and resistance to recombinant human erythropoietin therapy in hemodialysis patients. Am J Nephrol. 2008;28:935-40.
[16] Polańska B, Augustyniak D, Makulska I, Niemczuk M, Zwolińska D, Jankowski A. Elastase, α1-proteinase inhibitor, and interleukin-8 in pre-dialyzed and hemodialyzed patients with chronic kidney disease. Pediatr Int. 2010;52:735-43.
[17] Buchstein N, Hoffmann D, Smola H, Lang S, Paulsson M, Niemann C, et al. Alternative proteolytic processing of hepatocyte growth factor during wound repair. Am J Pathol. 2009;174:2116-28.
[18] Nakamura T, Sakai K, Matsumoto K. Hepatocyte growth factor twenty years on: Much more than a growth factor. J Gastroenterol Hepatol. 2011;26 Suppl 1:188-202.
[19] Liu KX, Kato Y, Narukawa M, Kim DC, Hanano M, Higuchi O, et al. Importance of the liver in plasma clearance of hepatocyte growth factors in rats. Am J Physiol. 1992;263:G642-9.
[20] Nakamura T, Teramoto H, Ichihara A. Purification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures. Proc Natl Acad Sci U S A. 1986;83:6489-93.
[21] Karihaloo A, Kale S, Rosenblum ND, Cantley LG. Hepatocyte growth factor-mediated renal epithelial branching morphogenesis is regulated by glypican-4 expression. Mol Cell Biol. 2004;24:8745-52.
[22] Rubin JS, Day RM, Breckenridge D, Atabey N, Taylor WG, Stahl SJ, et al. Dissociation of heparan sulfate and receptor binding domains of hepatocyte growth factor reveals that heparan sulfate-c-met interaction facilitates signaling. J Biol Chem. 2001;276:32977-83.
[23] Sakata H, Stahl SJ, Taylor WG, Rosenberg JM, Sakaguchi K, Wingfield PT, et al. Heparin binding and oligomerization of hepatocyte growth factor/scatter factor isoforms. Heparan sulfate glycosaminoglycan requirement for Met binding and signaling. J Biol Chem. 1997;272:9457-63.
[24] Liu KX, Kato Y, Kato M, Kaku TI, Nakamura T, Sugiyama Y. Existence of two nonlinear elimination mechanisms for hepatocyte growth factor in rats. Am J Physiol. 1997;273:E891-7.
[25] Nayeri F, Olsson H, Peterson C, Sundqvist T. Hepatocyte growth factor; expression, concentration and biological activity in chronic leg ulcers. J Dermatol Sci. 2005;37:75-85.
[26] Funakoshi H, Nakamura T. Hepatocyte growth factor: from diagnosis to clinical applications. Clin Chim Acta. 2003;327:1-23.
[27] Nagaraja C, Pradeep AR. Hepatocyte growth factor levels in gingival crevicular fluid in health, disease, and after treatment. J Periodontol. 2007;78:742-7.
[28] Nayeri F, Holmgren-Pettersson K, Perskvist N, Forsberg P, Peterson C, Sundqvist T. An in vitro model for assessment of the biological activity of hepatocyte growth factor. Growth Factors. 2007;25:33-40.
[29] Nayeri F, Nayeri T, Aili D, Brudin L, Liedberg B. Clinical impact of real-time evaluation of the biological activity and degradation of hepatocyte growth factor. Growth Factors. 2008;26:163-71.
[30] Ohnishi H, Mizuno S, Nakamura T. Inhibition of tubular cell proliferation by neutralizing endogenous HGF leads to renal hypoxia and bone marrow-derived cell engraftment in acute renal failure. Am J Physiol Renal Physiol. 2008;294:F326-35.
[31] Liu Y, Rajur K, Tolbert E, Dworkin LD. Endogenous hepatocyte growth factor ameliorates chronic renal injury by activating matrix degradation pathways. Kidney Int. 2000;58:2028-43.
[32] Gunnarsson P, Fornander L, Pahlsson P, Grenegard M. Sialic acid residues play a pivotal role in alpha(1)-acid glycoprotein (AGP)-induced generation of reactive oxygen species in chemotactic peptide pre-activated neutrophil granulocytes. Inflamm Res.59:89-95.
[33] Matsumoto K, Kataoka H, Date K, Nakamura T. Cooperative interaction between alpha- and beta-chains of hepatocyte growth factor on c-Met receptor confers ligand-induced receptor tyrosine phosphorylation and multiple biological responses. J Biol Chem. 1998; 273: 22913-20.
[34] Raymond WW, Cruz AC, Caughey GH. Mast cell and neutrophil peptidases attack an inactivation segment in hepatocyte growth factor to generate NK4-like antagonists. J Biol Chem. 2006; 281:1489-94.
[35] Uehara A, Muramoto K, Imamura T, Nakayama K, Potempa J, Travis J, et al. Arginine-specific gingipains from Porphyromonas gingivalis stimulate production of hepatocyte growth factor (scatter factor) through protease-activated receptors in human gingival fibroblasts in culture. J Immunol. 2005;175:6076-84.
[36] Howells GL, Macey MG, Chinni C, Hou L, Fox MT, Harriott P, et al. Proteinase-activated receptor-2: expression by human neutrophils. J Cell Sci. 1997;110 ( Pt 7):881-7.
[37] Dai C, Saleem MA, Holzman LB, Mathieson P, Liu Y. Hepatocyte growth factor signaling ameliorates podocyte injury and proteinuria. Kidney Int. 2010;77:962-73.
[38] Urbanek K, Rota M, Cascapera S, Bearzi C, Nascimbene A, De Angelis A, et al. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res. 2005;97:663-73.
[39] Nayeri F, Stromberg T, Larsson M, Brudin L, Soderstrom C, Forsberg P. Hepatocyte growth factor may accelerate healing in chronic leg ulcers: a pilot study. J Dermatolog Treat. 2002;13:81-6.

  
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