ABB  Vol.4 No.8 B , August 2013
Differences in the expression of hepatocyte growth factor in acute and chronic bowel inflammation—Implications for diagnosis?
ABSTRACT

Background: Hepatocyte growth factor (HGF) acts as an acute phase protein with regenerative properties. HGF is produced systemically and locally during inflammation but exhibits decreased binding affinity to heparan sulphate proteoglycan (HSPG)/glycosaminoglycan during chronic inflammation. We previously observed a high faecal concentration and binding affinity of HGF to HSPG during acute gastroenteritis. High faecal concentrations of calprotectin and HGF have been reported in chronic inflammatory bowel disease (IBD). Methods: Stool samples from patients with ulcerative colitis in remission (n = 11) or exacerbation (n = 5), microscopic colitis (n = 11), colon cancer (n = 6), or acute gastroenteritis caused by Clostridium difficile (n = 20), as well as healthy controls (n = 7), were analysed for the presence of HGF by ELISA, surface plasmon resonance, SDS-PAGE, and Western blot. Then in two patients with ulcerative colitis exacerbation and C. difficile infection, the expression of HGF and calprotectin was studied in colonic biopsies. Results: The faecal concentration of HGF was significantly higher in patients with ulcerative colitis compared to the other groups. The binding affinity to dextran was lower in all groups compared to acute inflammation. HGF receptor binding was similar across groups. In a patient with concomitant C. difficile infection and distal ulcerative colitis, HGF was highly expressed in the part of the bowel unaffected by ulcerative colitis, but no expression was found at the site of chronic inflammation. In the patient with total colitis the biopsies showed low expression of HGF. The areas with chronic inflammation exhibited infiltrating calprotectin-stained neutrophils. Conclusion: HGF is produced locally during inflammation of the bowel. The HGF produced during acute inflammation or exacerbations of chronic inflammation by the unaffected area shows binding affinity to glucosaminoglycans. Measuring HGF binding in faeces and biopsies may be a tool for differentiating between acute and chronic bowel inflammation, which should be assessed thoroughly in future studies.


Cite this paper
Lönn, J. , Nakka, S. , Olsson, H. , Bengtsson, T. , Almer, S. and Nayeri, F. (2013) Differences in the expression of hepatocyte growth factor in acute and chronic bowel inflammation—Implications for diagnosis?. Advances in Bioscience and Biotechnology, 4, 33-42. doi: 10.4236/abb.2013.48A2006.
References
[1]   Juckett G. and Trivedi, R. (2011) Evaluation of chronic diarrhea. American Family Physician, 84, 1119-1126.

[2]   Pardi, D.S. (2012) Miscellaneous colitides. Current Opinion in Gastroenterology, 28, 76-81. doi:10.1097/MOG.0b013e32834dda3b

[3]   Wilkins, T., Jarvis, K. and Patel, J. (2011) Diagnosis and management of Crohn’s disease. American Family Physician, 84, 1365-1375.

[4]   Grenier, A., Chollet-Martin, S., Crestani, B., Delarche, C., El Benna, J., Boutten, A., Andrieu, V., Durand, G., Gougerot-Pocidalo, M.A., Aubier, M. and Dehoux, M. (2002) Presence of a mobilizable intracellular pool of hepatocyte growth factor in human polymorphonuclear neutrophils. Blood, 99, 2997-3004. doi:10.1182/blood.V99.8.2997

[5]   Striz, I. and Trebichavsky, I. (2004) Calprotectin—A pleiotropic molecule in acute and chronic inflammation. Physiological Research, 53, 245-53.

[6]   Kumar, R.K. and Wakefield, D. (2001) Inflammation: Chronic. John Wiley & Sons, Ltd., Hoboken.

[7]   Cromer, W.E., Mathis, J.M., Granger, D.N., Chaitanya, G.V. and Alexander, J.S. (2011) Role of the endothelium in inflammatory bowel diseases. World Journal of Gastroenterology, 17, 578-593. doi:10.3748/wjg.v17.i5.578

[8]   Kostakis, I.D., Cholidou, K.G., Vaiopoulos, A.G., Vlachos, I.S., Perrea, D. and Vaos, G. (2012) Fecal calprotectin in pediatric inflammatory bowel disease: A systematic review. Digestive Diseases and Sciences, 58, 309-319. doi:10.1007/s10620-012-2347-5

[9]   Chen, C.C., Huang, J.L., Chang, C.J. and Kong, M.S. (2012) Fecal calprotectin as a correlative marker in clinical severity of infectious diarrhea and usefulness in evaluating bacterial or viral pathogens in children. Journal of Pediatric Gastroenterology and Nutrition, 55, 541-547. doi:10.1097/MPG.0b013e318262a718

[10]   Nakamura, T., Sakai, K. and Matsumoto, K. (2011) Hepatocyte growth factor twenty years on: Much more than a growth factor. Journal of Gastroenterology and Hepatology, 26, 188-202. doi:10.1111/j.1440-1746.2010.06549.x

[11]   Doeppner, T.R., Kaltwasser, B., ElAli, A., Zechariah, A., Hermann, D.M. and Bahr, M. (2011) Acute hepatocyte growth factor treatment induces long-term neuroprotection and stroke recovery via mechanisms involving neural precursor cell proliferation and differentiation. Journal of Cerebral Blood Flow & Metabolism, 31, 1251-62. doi:10.1038/jcbfm.2010.211

[12]   Nayeri, F., Stromberg, T., Larsson, M., Brudin, L., Soderstrom, C. and Forsberg, P. (2002) Hepatocyte growth factor may accelerate healing in chronic leg ulcers: A pilot study. Journal of Dermatological Treatment, 13, 81-86. doi:10.1080/095466302317584449

[13]   Derksen, P.W., Keehnen, R.M., Evers, L.M., van Oers, M.H., Spaargaren, M. and Pals, S.T. (2002) Cell surface proteoglycan syndecan-1 mediates hepatocyte growth factor binding and promotes Met signaling in multiple myeloma. Blood, 99, 1405-1410. doi:10.1182/blood.V99.4.1405

[14]   Hartmann, G., Prospero, T., Brinkmann, V., Ozcelik, O., Winter, G., Hepple, J., Batley, S., Bladt, F., Sachs, M., Birchmeier, C., Birchmeier, W. and Gherardi, E. (1998) Engineered mutants of HGF/SF with reduced binding to heparan sulphate proteoglycans, decreased clearance and enhanced activity in vivo. Current Biology, 8, 125-134. doi:10.1016/S0960-9822(98)70059-4

[15]   Liu, K.X., Kato, Y., Kato, M., Kaku, T.I., Nakamura, T. and Sugiyama, Y. (1997) Existence of two nonlinear elimination mechanisms for hepatocyte growth factor in rats. American Journal of Physiology, 273, E891-E897.

[16]   Liedberg, B., Nylander, C. and Lundstrom, I. (1995) Biosensing with surface plasmon resonance—How it all started. Biosensors and Bioelectronics, 10, i-ix. doi:10.1016/0956-5663(95)96965-2

[17]   Nayeri, F., Xu, J., Abdiu, A., Nayeri, T., Aili, D., Liedberg, B. and Carlsson, U. (2006) Autocrine production of biologically active hepatocyte growth factor (HGF) by injured human skin. Journal of Dermatological Science, 43, 49-56. doi:10.1016/j.jdermsci.2006.03.004

[18]   Nayeri, F., Nayeri, T., Aili, D., Brudin, L. and Liedberg, B. (2008) Clinical impact of real-time evaluation of the biological activity and degradation of hepatocyte growth factor. Growth Factors, 26, 163-171. doi:10.1080/08977190802128083

[19]   Berger, M., Welle, A., Gottwald, E., Rapp, M. and Lange, K. (2010) Biosensors coated with sulfated polysaccharides for the detection of hepatocyte growth factor/scatter factor in cell culture medium. Biosensors and Bioelectronics, 26, 1706-1709. doi:10.1016/j.bios.2010.07.065

[20]   Yamaji, N., Ido, A., Moriuchi, A., Numata, M., Setoyama, H., Tamai, T., Funakawa, K., Fujita, H., Sakiyama, T., Uto, H., Oketani, M. and Tsubouchi, H. (2011) Hepatocyte growth factor ameliorates mucosal injuries leading to inhibition of colon cancer development in mice. Oncology Reports, 26, 335-341.

[21]   Linares, P.M. and Gisbert, J.P. (2011) Role of growth factors in the development of lymphangiogenesis driven by inflammatory bowel disease: A review. Inflammatory Bowel Diseases, 17, 1814-1821. doi:10.1002/ibd.21554

[22]   Cammarota, R., Bertolini, V., Pennesi, G., Bucci, E.O., Gottardi, O., Garlanda, C., Laghi, L., Barberis, M.C., Sessa, F., Noonan, D.M. and Albini, A. (2010) The tumor microenvironment of colorectal cancer: Stromal TLR-4 expression as a potential prognostic marker. Journal of Translational Medicine, 8, 112. doi:10.1186/1479-5876-8-112

[23]   Nayeri, F., Almer, S., Brudin, L., et al. (2003) High heaptocyte growth factor levels in faeces during acute infectious gastroenteritis. Scandinavian Journal of Infectious Diseases, 35, 858-862. doi:10.1080/00365540310016484

[24]   Nayeri, F., Nilsson, I., Brudin, L. and Almer, S. (2004) Stability of faecal hepatocyte growth factor determination. Scandinavian Journal of Clinical & Laboratory Investigation, 64, 589-597. doi:10.1080/00365510410002850

[25]   Nayeri, F., Aili, D., Nayeri, T., Xu, J., Almer, S., Lundstrom, I., Akerlind, B. and Liedberg, B. (2005) Hepatocyte growth factor (HGF) in fecal samples: Rapid detection by surface plasmon resonance. BMC Gastroenterology, 5, 13. doi:10.1186/1471-230X-5-13

[26]   Rubin, J.S., Day, R.M., Breckenridge, D., Atabey, N., Taylor, W.G., Stahl, S.J., Wingfield, P.T., Kaufman, J.D., Schwall, R. and Bottaro, D.P. (2001) Dissociation of heparan sulfate and receptor binding domains of hepatocyte growth factor reveals that heparan sulfate-c-met interaction facilitates signaling. The Journal of Biological Chemistry, 276, 32977-32983. doi:10.1074/jbc.M105486200

[27]   Lonn, J., Almroth, G., Brudin, L. and Nayeri, F. (2012) An Antithrombin III product containing biologically active hepatocyte growth factor may be beneficial in deep ulcer infections. Cytokine, 60, 478-486. doi:10.1016/j.cyto.2012.05.023

[28]   Nayeri, F., Holmgren-Pettersson, K., Perskvist, N., Forsberg, P., Peterson, C. and Sundqvist, T. (2007) An in vitro model for assessment of the biological activity of hepatocyte growth factor. Growth Factors, 25, 33-40. doi:10.1080/08977190600997200

[29]   Wang, X., DeFrances, M.C., Dai, Y., Pediaditakis, P., Johnson, C., Bell, A., Michalopoulos, G.K. and Zarnegar, R. (2002) A mechanism of cell survival: Sequestration of Fas by the HGF receptor Met. Molecular Cell, 9, 411-421. doi:10.1016/S1097-2765(02)00439-2

[30]   Defrances, M.C., Wolf, H.K., Michalopoulos, G.K. and Zarnegar, R. (1992) The presence of hepatocyte growth factor in the developing rat. Development, 116, 387-395.

[31]   Lonn, 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

[32]   Lonn, J., Starkhammar Johansson, C., Kalvegren, H., Brudin, L., Skoglund, C., Garvin, P., Sarndahl, E., Ravald, N., Richter, A., Bengtsson, T. and Nayeri, F. (2012) Hepatocyte growth factor in patients with coronary artery disease and its relation to periodontal condition. Results in Immunology, 2, 7-12. doi:10.1016/j.rinim.2011.12.002

[33]   Lonn, J., Starkhammar Johansson, C., Nakka, S., Palm, E., Bengtsson, T., Nayeri, F. and Ravald, N. (2013) High concentration but low biological activity of hepatocyte growth factor in patients with periodontitis. Journal of Periodontology. doi:10.1902/jop.2013.130003

[34]   Buchstein, N., Hoffmann, D., Smola, H., Lang, S., Paulsson, M., Niemann, C., Krieg, T. and Eming, S.A. (2009) Alternative proteolytic processing of hepatocyte growth factor during wound repair. American Journal of Pathology, 174, 2116-2128. doi:10.2353/ajpath.2009.080597

[35]   Abednazari, H., Xu, J., Millinger, E., Brudin, L., Forsberg, P. and Nayeri, F. (2006) Hepatocyte growth factor is a better indicator of therapeutic response than C-reactive protein within the first day of treatment in pneumonia. Chemotherapy, 52, 260-263. doi:10.1159/000094868

[36]   Uehara, Y., Mori, C., Noda, T., Shiota, K. and Kitamura, N. (2000) Rescue of embryonic lethality in hepatocyte growth factor/scatter factor knockout mice. Genesis, 27, 99-103. doi:10.1002/1526-968X(200007)27:3<99::AID-GENE20>3.0.CO;2-Y

[37]   Manolakis, A.C., Kapsoritakis, A.N., Tiaka, E.K. and Potamianos, S.P. (2011) Calprotectin, calgranulin C, and other members of the s100 protein family in inflammatory bowel disease. Digestive Diseases and Sciences, 56, 1601-1611. doi:10.1007/s10620-010-1494-9

 
 
Top