par 2 receptor

Summary

Summary: A G-protein-coupled, proteinase-activated receptor that is expressed in a variety of tissues including ENDOTHELIUM; LEUKOCYTES; and the GASTROINTESTINAL TRACT. The receptor is activated by TRYPSIN, which cleaves off the N-terminal peptide from the receptor. The new N-terminal peptide is a cryptic ligand for the receptor. The uncleaved receptor can also be activated by the N-terminal peptide present on the activated THROMBIN RECEPTOR and by small synthetic peptides that contain the unmasked N-terminal sequence.

Top Publications

  1. Ebeling C, Lam T, Gordon J, Hollenberg M, Vliagoftis H. Proteinase-activated receptor-2 promotes allergic sensitization to an inhaled antigen through a TNF-mediated pathway. J Immunol. 2007;179:2910-7 pubmed
    ..Interfering with this pathway may prove to be useful for the prevention or treatment of allergic diseases. ..
  2. Gatti R, Andre E, Amadesi S, Dinh T, Fischer A, Bunnett N, et al. Protease-activated receptor-2 activation exaggerates TRPV1-mediated cough in guinea pigs. J Appl Physiol (1985). 2006;101:506-11 pubmed
    ..PAR2 activation, by sensitizing TRPV1 in primary sensory neurons, may play a role in the exaggerated cough observed in certain airways inflammatory diseases such as asthma and chronic obstructive pulmonary disease. ..
  3. Seymour M, Binion D, Compton S, Hollenberg M, MacNaughton W. Expression of proteinase-activated receptor 2 on human primary gastrointestinal myofibroblasts and stimulation of prostaglandin synthesis. Can J Physiol Pharmacol. 2005;83:605-16 pubmed
    ..Activation of PAR2 on gastrointestinal myofibroblasts stimulates PGE2 synthesis via different pathways in the colon than in the esophagus and small intestine. ..
  4. Cenac N, Andrews C, Holzhausen M, Chapman K, Cottrell G, Andrade Gordon P, et al. Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Invest. 2007;117:636-47 pubmed
    ..Our study establishes that proteases are released in IBS and that they can directly stimulate sensory neurons and generate hypersensitivity symptoms through the activation of PAR2. ..
  5. Tennant G, Wadsworth R, Kennedy S. PAR-2 mediates increased inflammatory cell adhesion and neointima formation following vascular injury in the mouse. Atherosclerosis. 2008;198:57-64 pubmed
    ..Our data show that PAR-2 modulates inflammatory cell adhesion when stimulated and in mice lacking the PAR-2 receptor, adhesion to injured vessels is reduced with a consequent reduction in neointima formation. ..
  6. Su X, Camerer E, Hamilton J, Coughlin S, Matthay M. Protease-activated receptor-2 activation induces acute lung inflammation by neuropeptide-dependent mechanisms. J Immunol. 2005;175:2598-605 pubmed
    ..These effects were either partly or completely neuropeptide dependent, suggesting that PAR2 can cause lung inflammation by a neurogenic mechanism. ..
  7. Page K, Hughes V, Bennett G, Wong H. German cockroach proteases regulate matrix metalloproteinase-9 in human bronchial epithelial cells. Allergy. 2006;61:988-95 pubmed
    ..As exposure to cockroaches is an environmental risk factor for asthma, we sought to investigate the role of German cockroach fecal remnants (frass) on MMP-9 expression...
  8. Fujimoto D, Hirono Y, Goi T, Katayama K, Hirose K, Yamaguchi A. Expression of protease activated receptor-2 (PAR-2) in gastric cancer. J Surg Oncol. 2006;93:139-44 pubmed
    ..4%) patients. We found a significant correlation between PAR-2 immunostaining and trypsin immunostaining. The results of this study lead us to believe that expression of PAR-2 is concerned with progression of gastric cancer. ..
  9. Hyun E, Andrade Gordon P, Steinhoff M, Vergnolle N. Protease-activated receptor-2 activation: a major actor in intestinal inflammation. Gut. 2008;57:1222-9 pubmed publisher
    ..Endogenous PAR(2) activation controls leukocyte recruitment in the colon and thus appears as a new potential therapeutic target for the treatment of inflammatory bowel disease. ..

More Information

Publications62

  1. Kim M, Choi B, Jung S, Sernka T, Kim S, Kim K, et al. Protease-activated receptor-2 increases exocytosis via multiple signal transduction pathways in pancreatic duct epithelial cells. J Biol Chem. 2008;283:18711-20 pubmed publisher
    ..Thus, in PDEC, PAR-2 activation increases [Ca(2+)](i) and activates PKC to stimulate exocytosis and mucin secretion. These functions may mediate the reported protective role of PAR-2 in different models of pancreatitis...
  2. Bushell T, Plevin R, Cobb S, Irving A. Characterization of proteinase-activated receptor 2 signalling and expression in rat hippocampal neurons and astrocytes. Neuropharmacology. 2006;50:714-25 pubmed
    ..Given the importance of Ca(2+) signalling in hippocampal synaptic plasticity and neurodegeneration, PAR2 may play a key modulatory role in these processes. ..
  3. Busso N, Frasnelli M, Feifel R, Cenni B, Steinhoff M, Hamilton J, et al. Evaluation of protease-activated receptor 2 in murine models of arthritis. Arthritis Rheum. 2007;56:101-7 pubmed
    ..Expression of PAR-2 in RA synovium was significantly higher than that in OA synovium, and this suggests that PAR-2 is implicated in the pathogenesis of immune-mediated forms of arthritis. ..
  4. Kelso E, Ferrell W, Lockhart J, Elias Jones I, Hembrough T, Dunning L, et al. Expression and proinflammatory role of proteinase-activated receptor 2 in rheumatoid synovium: ex vivo studies using a novel proteinase-activated receptor 2 antagonist. Arthritis Rheum. 2007;56:765-71 pubmed
    ..These findings identify PAR-2 as a novel upstream regulator of proinflammatory cytokine production in RA and indicate its potential as a novel therapeutic target in inflammatory arthritis. ..
  5. Johansson U, Lawson C, Dabare M, Syndercombe Court D, Newland A, Howells G, et al. Human peripheral blood monocytes express protease receptor-2 and respond to receptor activation by production of IL-6, IL-8, and IL-1{beta}. J Leukoc Biol. 2005;78:967-75 pubmed
    ..The results presented thus suggest that PAR-2 contributes to inflammatory responses by inducing the production of proinflammatory cytokines in peripheral blood monocytes. ..
  6. Jin G, Hayashi T, Kawagoe J, Takizawa T, Nagata T, Nagano I, et al. Deficiency of PAR-2 gene increases acute focal ischemic brain injury. J Cereb Blood Flow Metab. 2005;25:302-13 pubmed
    ..These results show that the deficiency of PAR-2 gene increases the acute ischemic cerebral injury associating with suppression of neuronal ERK activation and reactive astroglial activation. ..
  7. van der Merwe J, Moreau F, MacNaughton W. Protease-activated receptor-2 stimulates intestinal epithelial chloride transport through activation of PLC and selective PKC isoforms. Am J Physiol Gastrointest Liver Physiol. 2009;296:G1258-66 pubmed publisher
    ..We conclude that basolateral PAR(2)-induced chloride secretion involves activation of PKCbetaI and PKCdelta via a PLC-dependent mechanism resulting in the stimulation of cRaf and ERK1/2 signaling. ..
  8. Xiang Y, Masuko Hongo K, Sekine T, Nakamura H, Yudoh K, Nishioka K, et al. Expression of proteinase-activated receptors (PAR)-2 in articular chondrocytes is modulated by IL-1beta, TNF-alpha and TGF-beta. Osteoarthritis Cartilage. 2006;14:1163-73 pubmed
    ..Overexpression of PAR-2 in OA chondrocytes is upregulated by proinflammatory cytokines IL-1beta and TNF-alpha, and down-regulated by regulatory cytokine TGF-beta1. PAR-2 may be involved in the pathogenesis of OA. ..
  9. Fukunaga R, Hirano K, Hirano M, Niiro N, Nishimura J, Maehara Y, et al. Upregulation of proteinase-activated receptors and hypercontractile responses precede development of arterial lesions after balloon injury. Am J Physiol Heart Circ Physiol. 2006;291:H2388-95 pubmed
    ..The local inflammation associated with the sham operation may also contribute to the receptor upregulation. ..
  10. Cattaruzza F, Cenac N, Barocelli E, Impicciatore M, Hyun E, Vergnolle N, et al. Protective effect of proteinase-activated receptor 2 activation on motility impairment and tissue damage induced by intestinal ischemia/reperfusion in rodents. Am J Pathol. 2006;169:177-88 pubmed
    ..PAR(2) might be a signaling system in the neuroimmune communication in intestinal ischemia/reperfusion. ..
  11. Abe K, Aslam A, Walls A, Sato T, Inoue H. Up-regulation of protease-activated receptor-2 by bFGF in cultured human synovial fibroblasts. Life Sci. 2006;79:898-904 pubmed
    ..An important role could be played by bFGF in the regulation of functional PAR-2 expression in cultured RA synovial fibroblasts. ..
  12. Dulon S, Leduc D, Cottrell G, D Alayer J, Hansen K, Bunnett N, et al. Pseudomonas aeruginosa elastase disables proteinase-activated receptor 2 in respiratory epithelial cells. Am J Respir Cell Mol Biol. 2005;32:411-9 pubmed
  13. Ishikawa C, Tsuda T, Konishi H, Nakagawa N, Yamanishi K. Tetracyclines modulate protease-activated receptor 2-mediated proinflammatory reactions in epidermal keratinocytes. Antimicrob Agents Chemother. 2009;53:1760-5 pubmed publisher
    ..These results suggest that tetracyclines attenuate the PAR2-IL-8 axis in keratinocytes and thereby effectively modulate proinflammatory responses in the skin. ..
  14. Kawabata A, Kawao N, Kitano T, Matsunami M, Satoh R, Ishiki T, et al. Colonic hyperalgesia triggered by proteinase-activated receptor-2 in mice: involvement of endogenous bradykinin. Neurosci Lett. 2006;402:167-72 pubmed
    ..Our data thus provide ultimate evidence for role of PAR2 in colonic hypersensitivity, and suggest involvement of the bradykinin-B2 pathway. ..
  15. Chignard M, Pidard D. Neutrophil and pathogen proteinases versus proteinase-activated receptor-2 lung epithelial cells: more terminators than activators. Am J Respir Cell Mol Biol. 2006;34:394-8 pubmed
    ..Some of these activating and disabling proteinases are produced by host cells and others by pathogens, and may be present in the airspaces under diverse pathophysiologic settings. ..
  16. Tanaka Y, Sekiguchi F, Hong H, Kawabata A. PAR2 triggers IL-8 release via MEK/ERK and PI3-kinase/Akt pathways in GI epithelial cells. Biochem Biophys Res Commun. 2008;377:622-626 pubmed publisher
    ..Together, PAR2 triggers IL-8 release via two independent signaling pathways, MEK/ERK and PI3-kinase/Akt, suggesting a role of PAR2 as a pro-inflammatory receptor in the GI tract. ..
  17. Noorbakhsh F, Vergnolle N, McArthur J, Silva C, Vodjgani M, Andrade Gordon P, et al. Proteinase-activated receptor-2 induction by neuroinflammation prevents neuronal death during HIV infection. J Immunol. 2005;174:7320-9 pubmed
    ..001). Thus, neuroinflammation can exert protective effects by which it induces PAR-2 expression with the ensuing abrogation of neuronal death. ..
  18. Luo W, Wang Y, Hanck T, Stricker R, Reiser G. Jab1, a novel protease-activated receptor-2 (PAR-2)-interacting protein, is involved in PAR-2-induced activation of activator protein-1. J Biol Chem. 2006;281:7927-36 pubmed
    ..Taken together, our data demonstrate that Jab1 is an important effector that mediates a novel signal transduction pathway for PAR-2-dependent gene expression. ..
  19. Morris D, Ding Y, Ricks T, Gullapalli A, Wolfe B, Trejo J. Protease-activated receptor-2 is essential for factor VIIa and Xa-induced signaling, migration, and invasion of breast cancer cells. Cancer Res. 2006;66:307-14 pubmed
  20. Kouzaki H, O Grady S, Lawrence C, Kita H. Proteases induce production of thymic stromal lymphopoietin by airway epithelial cells through protease-activated receptor-2. J Immunol. 2009;183:1427-34 pubmed publisher
    ..By promoting TSLP production in the airways, proteases associated with airborne allergens may facilitate the development and/or exacerbation of Th2-type airway inflammation, particularly in allergic individuals. ..
  21. Kanke T, Ishiwata H, Kabeya M, Saka M, Doi T, Hattori Y, et al. Binding of a highly potent protease-activated receptor-2 (PAR2) activating peptide, [3H]2-furoyl-LIGRL-NH2, to human PAR2. Br J Pharmacol. 2005;145:255-63 pubmed
    ..7 These studies indicate that [(3)H]2-furoyl-LIGRL-NH(2) binds to human PAR2 at its ligand-binding site. The use of this radioligand will be valuable for characterising chemicals that interact to PAR2. ..
  22. Sevastos J, Kennedy S, Davis D, Sam M, Peake P, Charlesworth J, et al. Tissue factor deficiency and PAR-1 deficiency are protective against renal ischemia reperfusion injury. Blood. 2007;109:577-83 pubmed
    ..These experiments indicate that increased TF activity after renal IR leads to increased CXC chemokine expression and subsequent neutrophil-mediated injury predominantly by thrombin-dependent PAR-1 signaling. ..
  23. Kanke T, Kabeya M, Kubo S, Kondo S, Yasuoka K, Tagashira J, et al. Novel antagonists for proteinase-activated receptor 2: inhibition of cellular and vascular responses in vitro and in vivo. Br J Pharmacol. 2009;158:361-71 pubmed publisher
    ..These peptide-mimetic PAR(2) antagonists could be useful in evaluating PAR(2)-mediated biological events and might lead to a new generation of therapeutically useful antagonists. ..
  24. Fyfe M, Bergström M, Aspengren S, Peterson A. PAR-2 activation in intestinal epithelial cells potentiates interleukin-1beta-induced chemokine secretion via MAP kinase signaling pathways. Cytokine. 2005;31:358-67 pubmed
    ..Thus, identifying antagonists to the PAR-2 receptor may be beneficial by inhibiting potentiation of a proinflammatory response, through inhibition of p38 and ERK MAP kinases. ..
  25. Goon Goh F, Sloss C, Cunningham M, Nilsson M, Cadalbert L, Plevin R. G-protein-dependent and -independent pathways regulate proteinase-activated receptor-2 mediated p65 NFkappaB serine 536 phosphorylation in human keratinocytes. Cell Signal. 2008;20:1267-74 pubmed publisher
    ..Overall these novel data demonstrate an IKK2-dependent, predominantly G-protein-independent pathway involved in PAR-2 regulation of NFkappaB phosphorylation in keratinocytes. ..
  26. Ritchie E, Saka M, MacKenzie C, Drummond R, Wheeler Jones C, Kanke T, et al. Cytokine upregulation of proteinase-activated-receptors 2 and 4 expression mediated by p38 MAP kinase and inhibitory kappa B kinase beta in human endothelial cells. Br J Pharmacol. 2007;150:1044-54 pubmed
    ..These data reveal for the first time the signalling events involved in the upregulation of both PAR2 and PAR4 during pro-inflammatory challenge. ..
  27. McGuire J, Van Vliet B, Gimenez J, King J, Halfyard S. Persistence of PAR-2 vasodilation despite endothelial dysfunction in BPH/2 hypertensive mice. Pflugers Arch. 2007;454:535-43 pubmed
    ..In BPH/2 mice, vascular smooth muscle relaxation by PAR-2 is well preserved despite the presence of hypertension and impaired vasodilation responses to acetylcholine and bradykinin. ..
  28. Moussa L, Apostolopoulos J, Davenport P, Tchongue J, Tipping P. Protease-activated receptor-2 augments experimental crescentic glomerulonephritis. Am J Pathol. 2007;171:800-8 pubmed
    ..PAR-2-mediated augmentation of renal plasminogen activator inhibitor expression and inhibition of matrix-metalloprotinase-9 activity may contribute to increased glomerular fibrin accumulation and glomerular injury in CGN. ..
  29. Ui H, Andoh T, Lee J, Nojima H, Kuraishi Y. Potent pruritogenic action of tryptase mediated by PAR-2 receptor and its involvement in anti-pruritic effect of nafamostat mesilate in mice. Eur J Pharmacol. 2006;530:172-8 pubmed
    ..1 ng/site) and compound 48/80 (10 microg/site). These results suggest that mast cell tryptase elicits itch through PAR-2 receptor and that NFM inhibits itch-associated responses mainly through the inhibition of mast cell tryptase. ..
  30. Wang P, DeFea K. Protease-activated receptor-2 simultaneously directs beta-arrestin-1-dependent inhibition and Galphaq-dependent activation of phosphatidylinositol 3-kinase. Biochemistry. 2006;45:9374-85 pubmed
  31. Caruso R, Pallone F, Fina D, Gioia V, Peluso I, Caprioli F, et al. Protease-activated receptor-2 activation in gastric cancer cells promotes epidermal growth factor receptor trans-activation and proliferation. Am J Pathol. 2006;169:268-78 pubmed
    ..These data show that PAR-2 is overexpressed in GC and suggest a role of PAR-2 in EGFR trans-activation and cell growth. ..
  32. Amadesi S, Cottrell G, Divino L, Chapman K, Grady E, Bautista F, et al. Protease-activated receptor 2 sensitizes TRPV1 by protein kinase Cepsilon- and A-dependent mechanisms in rats and mice. J Physiol. 2006;575:555-71 pubmed
    ..Thus, PAR2 activates PKCepsilon and PKA in sensory neurons, and thereby sensitizes TRPV1 to cause thermal hyperalgesia. These mechanisms may underlie inflammatory pain, where multiple proteases are generated and released. ..
  33. Kelso E, Lockhart J, Hembrough T, Dunning L, Plevin R, Hollenberg M, et al. Therapeutic promise of proteinase-activated receptor-2 antagonism in joint inflammation. J Pharmacol Exp Ther. 2006;316:1017-24 pubmed
    ..Our findings represent a major advance in collectively identifying PAR2 as a novel target for the future treatment of arthritis. ..
  34. Chiu L, Perng D, Yu C, Su S, Chow L. Mold allergen, pen C 13, induces IL-8 expression in human airway epithelial cells by activating protease-activated receptor 1 and 2. J Immunol. 2007;178:5237-44 pubmed
    ..These finding show that Pen c 13 induces IL-8 release in airway epithelial cells and that this is dependent on PAR-1 and PAR-2 activation and intracellular calcium. ..
  35. Syeda F, Grosjean J, Houliston R, Keogh R, Carter T, Paleolog E, et al. Cyclooxygenase-2 induction and prostacyclin release by protease-activated receptors in endothelial cells require cooperation between mitogen-activated protein kinase and NF-kappaB pathways. J Biol Chem. 2006;281:11792-804 pubmed
  36. Camerer E, Cornelissen I, Kataoka H, Duong D, Zheng Y, Coughlin S. Roles of protease-activated receptors in a mouse model of endotoxemia. Blood. 2006;107:3912-21 pubmed
    ..These results raise the possibility that decreases in platelet count in the setting of sepsis may not be caused by disseminated intravascular coagulation but instead report on a sometimes parallel but independent process. ..
  37. van der Merwe J, Hollenberg M, MacNaughton W. EGF receptor transactivation and MAP kinase mediate proteinase-activated receptor-2-induced chloride secretion in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2008;294:G441-51 pubmed
    ..The secretory effect involves EGFR transactivation by Src, leading to subsequent ERK1/2 activation and increased cyclooxygenase activity. ..
  38. McGuire J, Hollenberg M, Bennett B, Triggle C. Hyperpolarization of murine small caliber mesenteric arteries by activation of endothelial proteinase-activated receptor 2. Can J Physiol Pharmacol. 2004;82:1103-12 pubmed
    ..Indeed, this hyperpolarization may be a primary mechanism for PAR-2-induced hypotension in vivo. ..
  39. Ostrowska E, Sokolova E, Reiser G. PAR-2 activation and LPS synergistically enhance inflammatory signaling in airway epithelial cells by raising PAR expression level and interleukin-8 release. Am J Physiol Lung Cell Mol Physiol. 2007;293:L1208-18 pubmed
    ..In summary, these results underline the important role of PAR-2 in human lung epithelial cells. Moreover, our study shows an intricate interplay between LPS and PAR agonists in affecting PAR regulation and IL-8 production. ..
  40. Kumar P, Lau C, Mathur M, Wang P, Defea K. Differential effects of beta-arrestins on the internalization, desensitization and ERK1/2 activation downstream of protease activated receptor-2. Am J Physiol Cell Physiol. 2007;293:C346-57 pubmed
    ..Together, these data suggest distinct temporal and functional roles for beta-arrestins in PAR-2 signaling, desensitization, and internalization. ..
  41. Knecht W, Cottrell G, Amadesi S, Mohlin J, Skåregärde A, Gedda K, et al. Trypsin IV or mesotrypsin and p23 cleave protease-activated receptors 1 and 2 to induce inflammation and hyperalgesia. J Biol Chem. 2007;282:26089-100 pubmed
    ..Thus, trypsin IV and p23 are inhibitor-resistant trypsins that can cleave and activate PARs, causing PAR(1)- and PAR(2)-dependent inflammation and PAR(2)-dependent hyperalgesia. ..
  42. Rallabhandi P, Nhu Q, Toshchakov V, Piao W, Medvedev A, Hollenberg M, et al. Analysis of proteinase-activated receptor 2 and TLR4 signal transduction: a novel paradigm for receptor cooperativity. J Biol Chem. 2008;283:24314-25 pubmed publisher
    ..Our data suggest a unique interaction between two distinct innate immune response receptors and support a novel paradigm of receptor cooperativity in inflammatory responses. ..
  43. Oikonomopoulou K, Hansen K, Saifeddine M, Vergnolle N, Tea I, Blaber M, et al. Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs). Biol Chem. 2006;387:817-24 pubmed
    ..We propose that, like thrombin and trypsin, the kallikreins must now be considered as important 'hormonal' regulators of tissue function, very likely acting in part via PARs. ..
  44. Bushell T. The emergence of proteinase-activated receptor-2 as a novel target for the treatment of inflammation-related CNS disorders. J Physiol. 2007;581:7-16 pubmed
  45. Cleator J, Zhu W, Vaughan D, Hamm H. Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP. Blood. 2006;107:2736-44 pubmed
    ..Thus, WPBs are pharmacologically and morphologically heterogeneous, and distinct granule populations are susceptible to differential regulation. ..
  46. Noorbakhsh F, Tsutsui S, Vergnolle N, Boven L, Shariat N, Vodjgani M, et al. Proteinase-activated receptor 2 modulates neuroinflammation in experimental autoimmune encephalomyelitis and multiple sclerosis. J Exp Med. 2006;203:425-35 pubmed
    ..001) in WT animals. These findings reveal previously unreported pathogenic interactions between CNS PAR2 expression and neuroinflammation with ensuing demyelination and axonal injury. ..
  47. Seitz I, Hess S, Schulz H, Eckl R, Busch G, Montens H, et al. Membrane-type serine protease-1/matriptase induces interleukin-6 and -8 in endothelial cells by activation of protease-activated receptor-2: potential implications in atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27:769-75 pubmed
    ..MT-SP1/matriptase is expressed in monocytes, thus, interaction of monocytic MT-SP1/matriptase with endothelial PAR-2 may contribute to atherosclerosis. ..
  48. Lim S, Tennant G, Kennedy S, Wainwright C, Kane K. Activation of mouse protease-activated receptor-2 induces lymphocyte adhesion and generation of reactive oxygen species. Br J Pharmacol. 2006;149:591-9 pubmed
    ..The present study indicates that activation of PAR-2 may be an important factor in modulating lymphocyte adhesion and ROS generation. The results have implications for developing anti-inflammatory strategies. ..
  49. Gecse K, Roka R, Ferrier L, Leveque M, Eutamene H, Cartier C, et al. Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic lumenal factor impairing colonic permeability and sensitivity. Gut. 2008;57:591-9 pubmed publisher
    ..Elevated colonic lumenal serine protease activity of IBS-D patients evokes a PAR-2-mediated colonic epithelial barrier dysfunction and subsequent allodynia in mice, suggesting a novel organic background in the pathogenesis of IBS. ..
  50. Scott G, Leopardi S, Printup S, Malhi N, Seiberg M, Lapoint R. Proteinase-activated receptor-2 stimulates prostaglandin production in keratinocytes: analysis of prostaglandin receptors on human melanocytes and effects of PGE2 and PGF2alpha on melanocyte dendricity. J Invest Dermatol. 2004;122:1214-24 pubmed
  51. Olejar T, Matej R, Zadinova M, Pouckova P. Proteinase-activated receptor-2 expression on cerebral neurones after radiation damage: immunohistochemical observation in Wistar rats. Int J Tissue React. 2002;24:81-8 pubmed
  52. Dulon S, Cande C, Bunnett N, Hollenberg M, Chignard M, Pidard D. Proteinase-activated receptor-2 and human lung epithelial cells: disarming by neutrophil serine proteinases. Am J Respir Cell Mol Biol. 2003;28:339-46 pubmed
    ..These findings suggest that the neutrophil serine proteinases may play a role in PAR-2-mediated lung inflammation. ..
  53. Masamune A, Kikuta K, Satoh M, Suzuki N, Shimosegawa T. Protease-activated receptor-2-mediated proliferation and collagen production of rat pancreatic stellate cells. J Pharmacol Exp Ther. 2005;312:651-8 pubmed
    ..Taken together, our results suggest a role of PAR-2 in the sustenance of pancreatic fibrosis through the increased proliferation and collagen production in PSCs. ..