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Protease-Activated Receptor Signaling in Lung Pathology

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Pathophysiological Aspects of Proteases

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Abstract

Protease-activated receptors (PARs) are self-activated G-protein-coupled receptors that have diverse roles in several disease paradigms including neurodegeneration, cancer, cardiovascular diseases, and others. Recently, extensive research on PAR family and its effect in modulating signaling pathways have gained attention. There is evidence that PARs are expressed in the airways in a variety of cell types that are relevant to inflammatory lung diseases, and activation of these receptors might be linked to significant pathological changes. Thus, PARs are exciting targets in lung disease research. This chapter mainly focuses on the role of PAR family members in several lung diseases. In this context, modulation of PAR signaling might open novel avenues in the treatment interventions in a number of respiratory conditions at least in part to reduce the burden of the diseases.

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References

  1. Fogarty AW, Lewis SA, McKeever TM, Lowe GD, Clark L, Britton J (2010) The association between blood coagulation activity and lung function: a population-based study. PLoS ONE 5(11):e15014

    Article  Google Scholar 

  2. Lane DA, Philippou H, Huntington JA (2005) Directing thrombin. Blood 106(8):2605–2612

    Article  CAS  Google Scholar 

  3. Kipnis E, Guery BP, Tournoys A, Leroy X, Robriquet L, Fialdes P, Neviere R, Fourrier F (2004) Massive alveolar thrombin activation in pseudomonas aeruginosa-induced acute lung injury. Shock 21(5):444–451

    Article  CAS  Google Scholar 

  4. Vu TK, Hung DT, Wheaton VI, Coughlin SR (1991) Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 64(6):1057–1068

    Article  CAS  Google Scholar 

  5. Coughlin SR (2000) Thrombin signaling and protease-activated receptors. Nature 407(6801):258–264

    Article  CAS  Google Scholar 

  6. Ramachandran R, Hollenberg MD (2008) Proteinases and signalling: pathophysiological and therapeutic implications via PARs and more. Br J Pharmacol 153(Suppl 1):S263–S282

    CAS  PubMed  Google Scholar 

  7. Kawabata A, Nishikawa H, Saitoh H, Nakaya Y, Hiramatsu K, Kubo S, Nishida M, Kawao N, Kuroda R, Sekiguchi F, Kinoshita M, Kakehi K, Arizono N, Yamagishi H, Kawai K (2004) A protective role of protease-activated receptor 1 in rat gastric mucosa. Gastroenterology 126(1):208–219

    Article  CAS  Google Scholar 

  8. Holzhausen M, Spolidorio LC, Ellen RP, Jobin MC, Steinhoff M, Andrade-Gordon P, Vergnolle N (2006) Protease-activated receptor-2 activation: a major role in the pathogenesis of porphyromonas gingivalis infection. Am J Pathol 168(4):1189–1199

    Article  CAS  Google Scholar 

  9. Sokolova E, Reiser G (2007) A novel therapeutic target in various lung diseases: airway proteases and protease-activated receptors. Pharmacol Ther 115(1):70–83

    Article  CAS  Google Scholar 

  10. Lee NR, Baek SY, Gu A, da Kim H, Kim SY, Lee JS, Kim IS (2016) House dust mite allergen suppresses neutrophil apoptosis by cytokine release via PAR2 in normal and allergic lymphocytes. Immunol Res 64(1):123–132

    Article  CAS  Google Scholar 

  11. Kalayarasan S, Sriram N, Soumyakrishnan S, Sudhandiran G (2013) Diallylsulfide attenuates excessive collagen production and apoptosis in a rat model of bleomycin induced pulmonary fibrosis through the involvement of protease activated receptor-2. Toxicol Appl Pharmacol 271(2):184–195

    Article  CAS  Google Scholar 

  12. Molino M, Barnathan ES, Numerof R, Clark J, Dreyer M, Cumashi A, Hoxie JA, Schechter N, Woolkalis M, Brass LF (1997) Interactions of mast cell tryptase with thrombin receptors and PAR-2. J Biol Chem 272(7):4043–4049

    Article  CAS  Google Scholar 

  13. Camerer E, Huang W, Coughlin SR (2000) Tissue factor- and factor X-dependent activation of protease-activated receptor 2 by factor VIIa. Proc Natl Acad Sci U S A 97(10):5255–5260

    Article  CAS  Google Scholar 

  14. Macfarlane SR, Seatter MJ, Kanke T, Hunter GD, Plevin R (2001) Proteinase-activated receptors. Pharmacol Rev 53(2):245–282

    CAS  PubMed  Google Scholar 

  15. Trejo J, Connolly AJ, Coughlin SR (1996) The cloned thrombin receptor is necessary and sufficient for activation of mitogen-activated protein kinase and mitogenesis in mouse lung fibroblasts. Loss of responses in fibroblasts from receptor knockout mice. J Biol Chem 271(35):21536–21541

    Article  CAS  Google Scholar 

  16. Cunningham MA, Rondeau E, Chen X, Coughlin SR, Holdsworth SR, Tipping PG (2000) Protease-activated receptor 1 mediates thrombin-dependent, cell-mediated renal inflammation in crescentic glomerulonephritis. J Exp Med 191(3):455–462

    Article  CAS  Google Scholar 

  17. Nystedt S, Emilsson K, Wahlestedt C, Sundelin J (1994) Molecular cloning of a potential proteinase activated receptor. Proc Natl Acad Sci U S A 91(20):9208–9212

    Article  CAS  Google Scholar 

  18. Vergnolle N (2000) Review article: proteinase-activated receptors—novel signals for gastrointestinal pathophysiology. Aliment Pharmacol Ther 14(3):257–266

    Article  CAS  Google Scholar 

  19. D’Andrea MR, Derian CK, Leturcq D, Baker SM, Brunmark A, Ling P, Darrow AL, Santulli RJ, Brass LF, Andrade-Gordon P (1998) Characterization of protease-activated receptor-2 immunoreactivity in normal human tissues. J Histochem Cytochem 46(2):157–164

    Article  Google Scholar 

  20. Connolly AJ, Ishihara H, Kahn ML, Farese RV Jr, Coughlin SR (1996) Role of the thrombin receptor in development and evidence for a second receptor. Nature 381(6582):516–519

    Article  CAS  Google Scholar 

  21. Ishihara H, Connolly AJ, Zeng D, Kahn ML, Zheng YW, Timmons C, Tram T, Coughlin SR (1997) Protease-activated receptor 3 is a second thrombin receptor in humans. Nature 386(6624):502–506

    Article  CAS  Google Scholar 

  22. Kahn ML, Zheng YW, Huang W, Bigornia V, Zeng D, Moff S, Farese RV Jr, Tam C, Coughlin SR (1998) A dual thrombin receptor system for platelet activation. Nature 394(6694):690–694

    Article  CAS  Google Scholar 

  23. Bohm SK, McConalogue K, Kong W, Bunnett NW (1998) Proteinase-activated receptors: new functions for old enzymes. News Physiol Sci 13:231–240

    CAS  PubMed  Google Scholar 

  24. Dery O, Corvera CU, Steinhoff M, Bunnett NW (1998) Proteinase-activated receptors: novel mechanisms of signaling by serine proteases. Am J Physiol 274(6 Pt 1):C1429–C1452

    Article  CAS  Google Scholar 

  25. Nakanishi-Matsui M, Zheng YW, Sulciner DJ, Weiss EJ, Ludeman MJ, Coughlin SR (2000) PAR3 is a cofactor for PAR4 activation by thrombin. Nature 404(6778):609–613

    Article  CAS  Google Scholar 

  26. Kahn ML, Nakanishi-Matsui M, Shapiro MJ, Ishihara H, Coughlin SR (1999) Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest 103(6):879–887

    Article  CAS  Google Scholar 

  27. Ku DD, Dai J (1997) Expression of thrombin receptors in human atherosclerotic coronary arteries leads to an exaggerated vasoconstrictory response in vitro. J Cardiovasc Pharmacol 30(5):649–657

    Article  CAS  Google Scholar 

  28. Howell DC, Johns RH, Lasky JA, Shan B, Scotton CJ, Laurent GJ, Chambers RC (2005) Absence of proteinase-activated receptor-1 signaling affords protection from bleomycin-induced lung inflammation and fibrosis. Am J Pathol 166(5):1353–1365

    Article  CAS  Google Scholar 

  29. Cicala C, Spina D, Keir SD, Severino B, Meli R, Page CP, Cirino G (2001) Protective effect of a PAR2-activating peptide on histamine-induced bronchoconstriction in guinea-pig. Br J Pharmacol 132(6):1229–1234

    Article  CAS  Google Scholar 

  30. Cocks TM, Fong B, Chow JM, Anderson GP, Frauman AG, Goldie RG, Henry PJ, Carr MJ, Hamilton JR, Moffatt JD (1999) A protective role for protease-activated receptors in the airways. Nature 398(6723):156–160

    Article  CAS  Google Scholar 

  31. Schmidlin F, Amadesi S, Dabbagh K, Lewis DE, Knott P, Bunnett NW, Gater PR, Geppetti P, Bertrand C, Stevens ME (2002) Protease-activated receptor 2 mediates eosinophil infiltration and hyperreactivity in allergic inflammation of the airway. J Immunol 169(9):5315–5321

    Article  Google Scholar 

  32. Asokananthan N, Graham PT, Fink J, Knight DA, Bakker AJ, McWilliam AS, Thompson PJ, Stewart GA (2002) Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells. J Immunol 168(7):3577–3585

    Article  CAS  Google Scholar 

  33. Vliagoftis H, Schwingshackl A, Milne CD, Duszyk M, Hollenberg MD, Wallace JL, Befus AD, Moqbel R (2000) Proteinase-activated receptor-2-mediated matrix metalloproteinase-9 release from airway epithelial cells. J Allergy Clin Immunol 106(3):537–545

    Article  CAS  Google Scholar 

  34. Ricciardolo FL, Steinhoff M, Amadesi S, Guerrini R, Tognetto M, Trevisani M, Creminon C, Bertrand C, Bunnett NW, Fabbri LM, Salvadori S, Geppetti P (2000) Presence and bronchomotor activity of protease-activated receptor-2 in guinea pig airways. Am J Respir Crit Care Med 161(5):1672–1680

    Article  CAS  Google Scholar 

  35. Gordon JR, Zhang X, Stevenson K, Cosford K (2000) Thrombin induces IL-6 but not TNF alpha secretion by mouse mast cells: threshold-level thrombin receptor and very low level Fcepsilonri signaling synergistically enhance IL-6 secretion. Cell Immunol 205(2):128–135

    Article  CAS  Google Scholar 

  36. Vliagoftis H, Befus AD, Hollenberg MD, Moqbel R (2001) Airway epithelial cells release eosinophil survival-promoting factors (GM-CSF) after stimulation of proteinase-activated receptor 2. J Allergy Clin Immunol 107(4):679–685

    Article  CAS  Google Scholar 

  37. Sun G, Stacey MA, Schmidt M, Mori L, Mattoli S (2001) Interaction of mite allergens Der p3 and Der p9 with protease-activated receptor-2 expressed by lung epithelial cells. J Immunol 167(2):1014–1021

    Article  CAS  Google Scholar 

  38. Masoli M, Fabian D, Holt S, Beasley R (2004) The global burden of asthma: executive summary of the GINA dissemination committee report. Allergy 59(5):469–478

    Article  Google Scholar 

  39. Robinson C, Wan H, Winton HL (1998) Epithelial repair in asthma. Do the benefits of house dust mite avoidance result from proteinase avoidance? Clin Exp Allergy 28(5):530–533

    Article  CAS  Google Scholar 

  40. Wan H, Winton HL, Soeller C, Tovey ER, Gruenert DC, Thompson PJ, Stewart GA, Taylor GW, Garrod DR, Cannell MB, Robinson C (1999) Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions. J Clin Invest 104(1):123–133

    Article  CAS  Google Scholar 

  41. Winton HL, Wan H, Cannell MB, Thompson PJ, Garrod DR, Stewart GA, Robinson C (1998) Class specific inhibition of house dust mite proteinases which cleave cell adhesion, induce cell death and which increase the permeability of lung epithelium. Br J Pharmacol 124(6):1048–1059

    Article  CAS  Google Scholar 

  42. Terada M, Kelly EA, Jarjour NN (2004) Increased thrombin activity after allergen challenge: a potential link to airway remodeling? Am J Respir Crit Care Med 169(3):373–377

    Article  Google Scholar 

  43. Asaduzzaman M, Nadeem A, Arizmendi N, Davidson C, Nichols HL, Abel M, Ionescu L, Puttagunta L, Thebaud B, Gordon J, DeFea K, Hollenberg MD, Vliagoftis H (2015) Functional inhibition of PAR2 alleviates allergen-induced airway hyper responsiveness and inflammation. Clin Exp Allergy 45(12):1844–1855

    Article  CAS  Google Scholar 

  44. de Boer JD, Van’t Veer C, Stroo I, van der Meer AJ, de Vos AF, van der Zee JS, Roelofs JJ, van der Poll T (2014) Protease-activated receptor-2 deficient mice have reduced house dust mite-evoked allergic lung inflammation. Innate Immun 20(6):618–625

    Article  Google Scholar 

  45. Arizmendi NG, Abel M, Mihara K, Davidson C, Polley D, Nadeem A, El Mays T, Gilmore BF, Walker B, Gordon JR, Hollenberg MD, Vliagoftis H (2011) Mucosal allergic sensitization to cockroach allergens is dependent on proteinase activity and proteinase-activated receptor-2 activation. J Immunol 186(5):3164–3172

    Article  CAS  Google Scholar 

  46. Knight DA, Lim S, Scaffidi AK, Roche N, Chung KF, Stewart GA, Thompson PJ (2001) Protease-activated receptors in human airways: upregulation of PAR-2 in respiratory epithelium from patients with asthma. J Allergy Clin Immunol 108(5):797–803

    Article  CAS  Google Scholar 

  47. Trupin L, Earnest G, San Pedro M, Balmes JR, Eisner MD, Yelin E, Katz PP, Blanc PD (2003) The occupational burden of chronic obstructive pulmonary disease. Eur Respir J 22(3):462–469

    Article  CAS  Google Scholar 

  48. Gong JH, Cho IH, Shin D, Han SY, Park SH, Kang YH (2014) Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice. Lab Invest 94(3):297–308

    Article  CAS  Google Scholar 

  49. Matej R, Vasakova M, Kukal J, Sterclova M, Olejar T (2014) Higher TGF-β with lower CD124 and TSLP, but no difference in PAR-2 expression in bronchial biopsy of bronchial asthma patients in comparison with COPD patients. Appl Immunohistochem Mol Morphol 22(7):543–549

    Article  CAS  Google Scholar 

  50. Miotto D, Hollenberg MD, Bunnett NW, Papi A, Braccioni F, Boschetto P, Rea F, Zuin A, Geppetti P, Saetta M, Maestrelli P, Fabbri LM, Mapp CE (2002) Expression of protease activated receptor-2 (PAR-2) in central airways of smokers and non-smokers. Thorax 57(2):146–151

    Article  CAS  Google Scholar 

  51. Prikk K, Maisi P, Sepper R, Stenman UH, Salo T, Sorsa T (2001) Association of trypsin-2 with activation of gelatinase B and collagenase-2 in human bronchoalveolar lavage fluid in vivo. Ann Med 33(6):437–444

    Article  CAS  Google Scholar 

  52. Ashitani J, Mukae H, Arimura Y, Matsukura S (2002) Elevated plasma procoagulant and fibrinolytic markers in patients with chronic obstructive pulmonary disease. Intern Med 41(3):181–185

    Article  CAS  Google Scholar 

  53. Wynn TA (2011) Integrating mechanisms of pulmonary fibrosis. J Exp Med 208(7):1339–1350

    Article  CAS  Google Scholar 

  54. Cheresh P, Kim SJ, Tulasiram S, Kamp DW (2013) Oxidative stress and pulmonary fibrosis. Biochim Biophys Acta 1832(7):1028–1040

    Article  CAS  Google Scholar 

  55. Tzouvelekis A, Herazo-Maya J, Sakamoto K, Bouros D (2016) Biomarkers in the evaluation and management of idiopathic pulmonary fibrosis. Curr Top Med Chem 16(14):1587–1598

    Article  CAS  Google Scholar 

  56. Jones MG, Fletcher S, Richeldi L (2013) Idiopathic pulmonary fibrosis: recent trials and current drug therapy. Respiration 86(5):353–363

    Article  CAS  Google Scholar 

  57. Imokawa S, Sato A, Hayakawa H, Kotani M, Urano T, Takada A (1997) Tissue factor expression and fibrin deposition in the lungs of patients with idiopathic pulmonary fibrosis and systemic sclerosis. Am J Respir Crit Care Med 156(2 Pt 1):631–636

    Article  CAS  Google Scholar 

  58. Chambers RC (2003) Role of coagulation cascade proteases in lung repair and fibrosis. Eur Respir J Suppl 44:33s–35s

    Article  CAS  Google Scholar 

  59. Michelin E, Snijders D, Conte S, Dalla Via P, Tagliaferro T, Da Dalt L, Monciotti CM, Simioni P, Stefanutti G, Ghirardo V, Gamba P, Barbato A (2008) Procoagulant activity in children with community acquired pneumonia, pleural effusion and empyema. Pediatr Pulmonol 43(5):472–475

    Article  CAS  Google Scholar 

  60. Hernandez-Rodríguez NA, Cambrey AD, Harrison NK, Chambers RC, Gray AJ, Southcott AM, duBois RM, Black CM, Scully MF, McAnulty RJ (1995) Role of thrombin in pulmonary fibrosis. Lancet 346(8982):1071–1073

    Article  Google Scholar 

  61. Dik WA, Zimmermann LJ, Naber BA, Janssen DJ, van Kaam AH, Versnel MA (2003) Thrombin contributes to bronchoalveolar lavage fluid mitogenicity in lung disease of the premature infant. Pediatr Pulmonol 35(1):34–41

    Article  Google Scholar 

  62. Mercer PF, Johns RH, Scotton CJ, Krupiczojc MA, Königshoff M, Howell DC, McAnulty RJ, Das A, Thorley AJ, Tetley TD, Eickelberg O, Chambers RC (2009) Pulmonary epithelium is a prominent source of proteinase-activated receptor-1-inducible CCL2 in pulmonary fibrosis. Am J Respir Crit Care Med 179(5):414–425

    Article  Google Scholar 

  63. Ask K, Bonniaud P, Maass K, Eickelberg O, Margetts PJ, Warburton D, Groffen J, Gauldie J, Kolb M (2008) Progressive pulmonary fibrosis is mediated by TGF-beta isoform 1 but not TGF-beta3. Int J Biochem Cell Biol 40(3):484–495

    Article  CAS  Google Scholar 

  64. Jenkins RG, Su X, Su G, Scotton CJ, Camerer E, Laurent GJ, Davis GE, Chambers RC, Matthay MA, Sheppard D (2006) Ligation of protease-activated receptor 1 enhances alpha(v)beta6 integrin-dependent TGF-beta activation and promotes acute lung injury. J Clin Invest 116(6):1606–1614

    Article  CAS  Google Scholar 

  65. Soumyakrishnan S, Divya T, Kalayarasan S, Sriram N, Sudhandiran G (2014) Daidzein exhibits anti-fibrotic effect by reducing the expressions of proteinase activated receptor 2 and TGFβ1/smad mediated inflammation and apoptosis in Bleomycin-induced experimental pulmonary fibrosis. Biochimie 103:23–36

    Article  CAS  Google Scholar 

  66. Ando S, Otani H, Yagi Y, Kawai K, Araki H, Fukuhara S, Inagaki C (2007) Proteinase-activated receptor 4 stimulation-induced epithelial-mesenchymal transition in alveolar epithelial cells. Respir Res 8:31

    Article  Google Scholar 

  67. Mokra D, Kosutova P (2015) Biomark Acute Lung Inj. Respir Physiol Neurobiol 209:52–58

    Article  CAS  Google Scholar 

  68. Günther A, Mosavi P, Heinemann S, Ruppert C, Muth H, Markart P, Grimminger F, Walmrath D, Temmesfeld-Wollbrück B, Seeger W (2000) Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome. Am J Respir Crit Care Med 161(2 Pt 1):454–462

    Article  Google Scholar 

  69. Su X, Matthay MA (2009) Role of protease activated receptor 2 in experimental acute lung injury and lung fibrosis. Anat Rec (Hoboken) 292(4):580–586

    Article  Google Scholar 

  70. Gan X, Liu D, Huang P, Gao W, Chen X, Hei Z (2012) Mast-cell-releasing tryptase triggers acute lung injury induced by small intestinal ischemia-reperfusion by activating PAR-2 in rats. Inflammation 35(3):1144–1153

    Article  CAS  Google Scholar 

  71. Scotton CJ, Krupiczojc MA, Königshoff M, Mercer PF, Lee YC, Kaminski N, Morser J, Post JM, Maher TM, Nicholson AG, Moffatt JD, Laurent GJ, Derian CK, Eickelberg O, Chambers RC (2009) Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury. J Clin Invest 119(9):2550–2563

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Dasgupta A, Neighbour H, Nair P (2013) Targeted therapy of bronchitis in obstructive airway diseases. Pharmacol Ther 140(3):213–222

    Article  CAS  Google Scholar 

  73. Naldini A, Sower L, Bocci V, Meyers B, Carney DH (1998) Thrombin receptor expression and responsiveness of human monocytic cells to thrombin is linked to interferon-induced cellular differentiation. J Cell Physiol 177(1):76–84

    Article  CAS  Google Scholar 

  74. Takizawa T, Tamiya M, Hara T, Matsumoto J, Saito N, Kanke T, Kawagoe J, Hattori Y (2005) Abrogation of bronchial eosinophilic inflammation and attenuated eotaxin content in protease-activated receptor 2-deficient mice. J Pharmacol Sci 98(1):99–102

    Article  CAS  Google Scholar 

  75. Su X, Camerer E, Hamilton JR, Coughlin SR, Matthay MA (2005) Protease-activated receptor-2 activation induces acute lung inflammation by neuropeptide-dependent mechanisms. J Immunol 175(4):2598–2605

    Article  CAS  Google Scholar 

  76. Vancheri C, Mastruzzo C, Sortino MA, Crimi N (2004) The lung as a privileged site for the beneficial actions of PGE2. Trends Immunol 25(1):40–46

    Article  CAS  Google Scholar 

  77. Sokolova E, Hartig R, Reiser G (2008) Downregulation of protease-activated receptor-1 in human lung fibroblasts is specifically mediated by the prostaglandin E receptor EP2 through cAMP elevation and protein kinase A. FEBS J 275(14):3669–3679

    Article  CAS  Google Scholar 

  78. D’Agostino B, Roviezzo F, De Palma R, Terracciano S, De Nardo M, Gallelli L, Abbate GF, D’Aiuto E, Russo M, Cirino G, Rossi F (2007) Activation of protease-activated receptor-2 reduces airways inflammation in experimental allergic asthma. Clin Exp Allergy 37(10):1436–1443

    PubMed  Google Scholar 

  79. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57(1):43–66

    Article  Google Scholar 

  80. Nierodzik ML, Chen K, Takeshita K, Li JJ, Huang YQ, Feng XS, D’Andrea MR, Andrade-Gordon P, Karpatkin S (1998) Protease-activated receptor 1 (PAR-1) is required and rate-limiting for thrombin-enhanced experimental pulmonary metastasis. Blood 92(10):3694–3700

    CAS  PubMed  Google Scholar 

  81. Henrikson KP, Salazar SL, Fenton JW 2nd, Pentecost BT (1999) Role of thrombin receptor in breast cancer invasiveness. Br J Cancer 79(3–4):401–406

    Article  CAS  Google Scholar 

  82. Boire A, Covic L, Agarwal A, Jacques S, Sherifi S, Kuliopulos A (2005) PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Cell 120(3):303–313

    Article  CAS  Google Scholar 

  83. Cisowski J, O’Callaghan K, Kuliopulos A, Yang J, Nguyen N, Deng Q, Yang E, Fogel M, Tressel S, Foley C, Agarwal A, Hunt SW 3rd, McMurry T, Brinckerhoff L, Covic L (2011) Targeting protease-activated receptor-1 with cell-penetrating pepducins in lung cancer. Am J Pathol 179(1):513–523

    Article  CAS  Google Scholar 

  84. Huang SH, Li Y, Chen HG, Rong J, Ye S (2013) Activation of proteinase-activated receptor 2 prevents apoptosis of lung cancer cells. Cancer Invest 31(9):578–581

    Article  CAS  Google Scholar 

  85. Zhu L, Wang X, Wu J, Mao D, Xu Z, He Z, Yu A (2012) Cooperation of protease-activated receptor 1 and integrin ανβ5 in thrombin-mediated lung cancer cell invasion. Oncol Rep 28(2):553–560

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank Indian Council of Medical Research for supporting a grant in Protease-activated receptor signaling in pulmonary fibrosis (52/21/2008-BMS).

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Authors and Affiliations

  1. Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai, India

    Ganapasam Sudhandiran, Srinivasan Kalayarasan, Thomas Divya & Bakthavatchalam Velavan

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  1. Ganapasam Sudhandiran
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  2. Srinivasan Kalayarasan
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  3. Thomas Divya
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  4. Bakthavatchalam Velavan
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Correspondence to Ganapasam Sudhandiran .

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  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Institute of Cardiovascular Sciences, University of Manitoba, Manitoba, Canada

    Naranjan S. Dhalla

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Sudhandiran, G., Kalayarasan, S., Divya, T., Velavan, B. (2017). Protease-Activated Receptor Signaling in Lung Pathology. In: Chakraborti, S., Dhalla, N. (eds) Pathophysiological Aspects of Proteases. Springer, Singapore. https://doi.org/10.1007/978-981-10-6141-7_23

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