Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2009, Vol. 3 Issue (3) : 309-315     DOI: 10.1007/s11684-009-0043-4
Research articles |
Gene and protein expression of proteinase-activated receptor-1, 2 in a murine model of acute graft host disease
Quan LI MD 1, Weiming LI MD 1, Ping ZOU MD 1, Jian ZHANG BM 2,
1.Institute of Hematology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; 2.Department of General Surgery, Xiangfan Central Hospital, Xiangfan 441021, China;
Download: PDF(326 KB)  
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract  Proteinase-activated receptors (PARs) are a novel subclass of seven transmembrane-spanning, G protein-coupled receptors. PAR-1 and PAR-2 are widely expressed in a variety of cells and are found to be involved in many physiological and pathological processes including inflammation and immune response. However, little is known about the function of PAR-1, 2 in acute graft vs host disease (GVHD). In the present study, we first detected the expression of PAR-1, 2 protein and mRNA in a murine model of acute GVHD using the methods of immunohistochemistry, Western blot and quantitative real-time polymerase chain reaction (PCR). Syngeneic hematopoietic stem cell transplantation (HSCT) mice served as controls. The relative gene expression level of PAR-1 was significantly increased in the skin, liver, small intestine of allogeneic HSCT mice (in skin: 0.039±0.013 vs 0.008±0.002 of controls, P=0.009; in liver: 0.165±0.006 vs 0.017±0.006 of controls, P=0.004; in small intestine: 0.215±0.009 vs 0.016±0.002 of controls, P=0.003), but not in the stomach, lung and kidney of allogeneic HSCT mice (P>0.05). PAR-2 mRNA expression in the liver and small intestine of allogeneic HSCT mice (in liver: 0.010±0.002 vs 0.003±0.001 of controls, P=0.008; in small intestine: 0.006±0.001 vs 0.003±0.001 of controls, P=0.024) was increased significantly, but PAR-2 mRNA expression in the other organs (P>0.05) was not found to be significantly elevated. PAR-1, 2 protein expression was in accordance with the mRNA expression, as shown by Western blot. Using immunohistochemistry the present study demonstrated that there was strong PAR-1, 2 immunoreactivity in the epithelial cell and vascular endothelial cell of target organs of acute GVHD. Our findings of markedly increased expression of PAR-1, 2 in target organs of acute GVHD suggest that PAR-1 and PAR-2 may play an important role in the pathogenesis of acute GVHD.
Keywords graft vs host disease      proteinase-activated receptor      murine model      hematopoietic stem cell transplantation      
Issue Date: 05 September 2009
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-009-0043-4     OR     http://academic.hep.com.cn/fmd/EN/Y2009/V3/I3/309
Toubai T, Tanaka J, Nishihira J, Ohkawara T, Hirate D, Kondo N, Tone S, Shono Y, Ibata M, Sugita J, Kato N, Miura Y, Iwao N, Ota S, Imamura M. Effect of macrophage migrationinhibitory factor (MIF) on acute graft-versus-host disease in a murinemodel of allogeneic stem cell transplantation. Transpl Immunol, 2006, 16(2): 117―124

doi: 10.1016/j.trim.2006.05.001
Reddy P, Ferrara J L. Immunobiology of acute graft-versus-hostdisease. Blood Rev, 2003, 17(4): 187―194

doi: 10.1016/S0268-960X(03)00009-2
Pober J S, Orosz C G, Rose M L, Savage C O. Can graft endothelial cells initiate a host anti-graft immune response? Transplantation, 1996, 61(3): 343―349

doi: 10.1097/00007890-199602150-00001
Schmidlin F, Bunnett N W. Protease-activated receptors:how proteases signal to cells. Curr OpinPharmacol, 2001, 1(6): 575―582

doi: 10.1016/S1471-4892(01)00099-6
Macfarlane S R, Seatter M J, Kanke T, Hunter G D, Plevin R. Proteinase-activated receptors. Pharmacol Rev, 2001, 53(2): 245―282
Ossovskaya V S, Bunnett N W. Protease-activated receptors:contribution to physiology and disease. Physiol Rev, 2004, 84(2): 579―621

doi: 10.1152/physrev.00028.2003
Zhao A, Morimoto M, Dawson H, Elfrey J E, Madden K B, Gause W C, Min B, Finkelman F D, Urban J F Jr, Shea-Donohue T. Immuneregulation of protease-activated receptor-1 expression in murine smallintestine during nippostrongylus brasiliensis infection. J Immunol, 2005, 175(4): 2563―2569
Fan Y, Zhang W, Mulholland M. Thrombin and PAR-1-AP increase proinflammatory cytokineexpression in C6 Cells. J Surg Res, 2005, 129(2): 196―201

doi: 10.1016/j.jss.2005.07.041
Coughlin S R. Protease-activated receptors in hemostasis, thrombosis and vascularbiology. J Thromb Haemost, 2005, 3(8): 1800―1814

doi: 10.1111/j.1538-7836.2005.01377.x
Vergnolle N, Wallace J L, Bunnett N W, Hollenberg M D. Protease-activated receptors in inflammation, neuronal signalingand pain. Trends Pharmacol Sci, 2001, 22(3): 146―152

doi: 10.1016/S0165-6147(00)01634-5
Cooke K R, Kobzik L, Martin T R, Brewer J, Delmonte J Jr, Crawford J M, Ferrara J L. An experimental model of idiopathic pneumonia syndrome after bonemarrow transplantation: I. The roles of minor H antigens and endotoxin. Blood, 1996, 88(8): 3230―3239
Ferrara J L, Levy R, Chao N J. Pathophysiologic mechanisms of acute graft-vs.-host disease. Biol Blood Marrow Transplant, 1999, 5(6): 347―356

doi: 10.1016/S1083-8791(99)70011-X
Hill G R, Ferrara J L. The primacy of the gastrointestinaltract as a target organ of acute graft-versus-host disease: rationalefor the use of cytokine shields in allogeneic bone marrow transplantation. Blood, 2000, 95(9): 2754―2759
Shlomchik W D, Couzens M S, Tang C B, McNiff J, Robert M E, Liu J. Prevention of graft-versus-host disease by inactivationof host antigen-presenting cells. Science, 1999, 285(5426): 412―415

doi: 10.1126/science.285.5426.412
Rullier A, Senant N, Kisiel W, Bioulac-Sage P, Balabaud C, Le Bail B, Rosenbaum J. Expressionof protease-activated receptors and tissue factor in human liver. Virchows Arch, 2006, 448(1): 46―51

doi: 10.1007/s00428-005-0078-0
Kauffman H F, Tomee J F, van de Riet M A, Timmerman A J, Borger P. Protease-dependent activationof epithelial cells by fungal allergens leads to morphologic changesand cytokine production. J Allergy ClinImmunol, 2000, 105(6): 1185―1193

doi: 10.1067/mai.2000.106210
Dumler J S, Beschorner W E, Farmer E R, Di Gennaro K A, Saral R, Santos G W. Endothelial-cell injury in cutaneous acute graft-versus-hostdisease. Am J Pathol, 1989, 135(6): 1097―1103
Sviland L, Sale G E, Myerson D. Endothelial changes in cutaneous graft-versus-host disease:a comparison between HLA matched and mismatched recipients of bonemarrow transplantation. Bone Marrow Transplant, 1991, 7(1): 35―38
Tesfamariam B, DeFelice A F. Endothelial injury in theinitiation and progression of vascular disorders. Vascul Pharmacol, 2007, 46(4): 229―237

doi: 10.1016/j.vph.2006.11.005
Goon P K, Boos C J, Lip G Y. Circulating endothelial cells: markers of vascular dysfunction. Clin Lab, 2005, 51(9,10): 531―538
Pihusch V, Rank A, Steber R, Pihusch M, Pihusch R, Toth B, Hiller E, Kolb H J. Endothelial cell-derivedmicroparticles in allogeneic hematopoietic stem cell recipients. Transplantation, 2006, 81(10): 1405―1409

doi: 10.1097/01.tp.0000209218.24916.ba
Kawagoe J, Takizawa T, Matsumoto J, Tamiya M, Meek S E, Smith A J, Hunter G D, Plevin R, Saito N, Kanke T, Fujii M, Wada Y. Effectof protease-activated receptor-2 deficiency on allergic dermatitisin the mouse ear. Jpn J Pharmacol, 2002, 88(1): 77―84

doi: 10.1254/jjp.88.77
Tichelli A, Gratwohl A. Vascular endothelium as ‘novel’target of graft-versus-host disease. BestPract Res Clin Haematol, 2008, 21(2): 139―148

doi: 10.1016/j.beha.2008.02.002
Biedermann B C. Vascular endothelium and graft-versus-host disease. Best Pract Res Clin Haematol, 2008, 21(2): 129―138

doi: 10.1016/j.beha.2008.02.003
Ahn H S, Chackalamannil S, Boykow G, Graziano M P, Foster C. Development of proteinase-activatedreceptor 1 antagonists as therapeutic agents for thrombosis, restenosisand inflammatory diseases. Curr Pharm Des, 2003, 9(28): 2349―2365

doi: 10.2174/1381612033453884
Ma L, Perini R, McKnight W, Dicay M, Klein A, Hollenberg M D, Wallace J L. Proteinase-activated receptors1 and 4 counter-regulate endostatin and VEGF release from human platelets. Proc Natl Acad Sci U S A, 2005, 102(1): 216―220

doi: 10.1073/pnas.0406682102
Zania P, Kritikou S, Flordellis C S, Maragoudakis M E, Tsopanoglou N E. Blockade of angiogenesisby small molecule antagonists to protease-activated receptor-1: associationwith endothelial cell growth suppression and induction of apoptosis. J Pharmacol Exp Ther, 2006, 318(1): 246―254

doi: 10.1124/jpet.105.099069
Andrade-Gordon P, Maryanoff B E, Derian C K, Zhang H C, Addo M F, Darrow A L, Eckardt A J, Hoekstra W J, McComsey D F, Oksenberg D, Reynolds E E, Santulli R J, Scarborough R M, Smith C E, White K B. Design, synthesis,and biological characterization of a peptide-mimetic antagonist fora tethered-ligand receptor. Proc Natl AcadSci U S A, 1999, 96(22): 12257―12262

doi: 10.1073/pnas.96.22.12257
Zhang H C, Derian C K, Andrade-Gordon P, Hoekstra W J, McComsey D F, White K B, Poulter B L, Addo M F, Cheung W M, Damiano B P, Oksenberg D, Reynolds E E, Pandey A, Scarborough R M, Maryanoff B E. Discovery and optimization of a novel series of thrombinreceptor (PAR-1) antagonists: potent, selective peptide mimetics basedon indole and indazole templates. J MedChem, 2001, 44(7): 1021―1024

doi: 10.1021/jm000506s
Suzuki T, Moraes T J, Vachon E, Ginzberg H H, Huang T T, Matthay M A, Hollenberg M D, Marshall J, McCulloch C A, Abreu M T, Chow C W, Downey G P. Proteinase-activated receptor-1 mediates elastase-induced apoptosisof human lung epithelial cells. Am J RespirCell Mol Biol, 2005, 33(3): 231―247

doi: 10.1165/rcmb.2005-0109OC
[1] Lanping Xu,Huanling Zhu,Jianda Hu,Depei Wu,Hao Jiang,Qian Jiang,Xiaojun Huang. Superiority of allogeneic hematopoietic stem cell transplantation to nilotinib and dasatinib for adult patients with chronic myelogenous leukemia in the accelerated phase[J]. Front. Med., 2015, 9(3): 304-311.
[2] Xiaodong Mo, Xiaojun Huang. Advancement of human leukocyte antigen-partially matched related hematopoietic stem cell transplantation[J]. Front Med, 2013, 7(3): 306-315.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed