F2rl1

Summary

Gene Symbol: F2rl1
Description: coagulation factor II (thrombin) receptor-like 1
Alias: Gpcr11, PAR-2, Par2, proteinase-activated receptor 2, G-protein coupled receptor 11, Protease-activated receptor-2, coagulation factor II receptor-like 1, thrombin receptor-like 1
Species: mouse
Products:     F2rl1

Top Publications

  1. 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. ..
  2. 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
    Proteinase-activated receptor 2 (PAR2), a seven-transmembrane G protein-coupled receptor, is activated at inflammatory sites by proteolytic cleavage of its extracellular N terminus by trypsin-like enzymes, exposing a tethered, receptor-..
  3. Kahn M, Hammes S, Botka C, Coughlin S. Gene and locus structure and chromosomal localization of the protease-activated receptor gene family. J Biol Chem. 1998;273:23290-6 pubmed
    ..The PAR1 gene is located centrally and is flanked upstream by the PAR3 gene and downstream by the PAR2 gene in both species...
  4. Hachem J, Houben E, Crumrine D, Man M, Schurer N, Roelandt T, et al. Serine protease signaling of epidermal permeability barrier homeostasis. J Invest Dermatol. 2006;126:2074-86 pubmed
  5. 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. ..
  6. Schaffner F, Versteeg H, Schillert A, Yokota N, Petersen L, Mueller B, et al. Cooperation of tissue factor cytoplasmic domain and PAR2 signaling in breast cancer development. Blood. 2010;116:6106-13 pubmed publisher
    ..In human breast cancer, TF and PAR2 are up-regulated and TF cytoplasmic domain phosphorylation is correlated with relapse...
  7. Nystedt S, Emilsson K, Wahlestedt C, Sundelin J. Molecular cloning of a potential proteinase activated receptor. Proc Natl Acad Sci U S A. 1994;91:9208-12 pubmed
    ..Because this, to our knowledge, is the second example, besides the thrombin receptor, of a proteolytically activated seven-transmembrane G-protein-coupled receptor, we have provisionally named it proteinase activated receptor 2.
  8. Seeliger S, Derian C, Vergnolle N, Bunnett N, Nawroth R, Schmelz M, et al. Proinflammatory role of proteinase-activated receptor-2 in humans and mice during cutaneous inflammation in vivo. FASEB J. 2003;17:1871-85 pubmed
    ..Thus, PAR-2 may be a beneficial therapeutic target for the treatment of inflammatory skin diseases. ..
  9. 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. ..

More Information

Publications79

  1. 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. ..
  2. Camerer E, Kataoka H, Kahn M, Lease K, Coughlin S. Genetic evidence that protease-activated receptors mediate factor Xa signaling in endothelial cells. J Biol Chem. 2002;277:16081-7 pubmed
    ..Protease-activated receptors (PAR1, PAR2, and PAR4) can mediate Xa signaling in heterologous expression systems...
  3. Lindner J, Kahn M, Coughlin S, Sambrano G, Schauble E, Bernstein D, et al. Delayed onset of inflammation in protease-activated receptor-2-deficient mice. J Immunol. 2000;165:6504-10 pubmed
    ..We hypothesized that activation of endothelial PAR2 by mast cell tryptase or other proteases also contributes to inflammatory responses...
  4. Page K, Ledford J, Zhou P, Dienger K, Wills Karp M. Mucosal sensitization to German cockroach involves protease-activated receptor-2. Respir Res. 2010;11:62 pubmed publisher
    ..The role for PAR-2 in mediating allergic airway inflammation has not been assessed using a real world allergen...
  5. Damiano B, Cheung W, Santulli R, Fung Leung W, Ngo K, Ye R, et al. Cardiovascular responses mediated by protease-activated receptor-2 (PAR-2) and thrombin receptor (PAR-1) are distinguished in mice deficient in PAR-2 or PAR-1. J Pharmacol Exp Ther. 1999;288:671-8 pubmed
    ..Moreover, the accentuated response to PAR-1 activation in PAR-2-deficient mice suggests a compensatory response and potential receptor cross-talk. ..
  6. Lewkowich I, Day S, Ledford J, Zhou P, Dienger K, Wills Karp M, et al. Protease-activated receptor 2 activation of myeloid dendritic cells regulates allergic airway inflammation. Respir Res. 2011;12:122 pubmed publisher
    ..Together these data suggest an important role for allergen activation of PAR-2 on mDCs in mediating Th2/Th17 cytokine production and allergic airway responses. ..
  7. 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
    ..We investigated the role of PAR2 in the pathogenesis of multiple sclerosis (MS) in humans and experimental autoimmune encephalomyelitis (EAE) in ..
  8. 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
    ..by a serine protease inhibitor and was absent in neurons lacking functional protease-activated receptor-2 (PAR2)...
  9. Uusitalo Jarvinen H, Kurokawa T, Mueller B, Andrade Gordon P, Friedlander M, Ruf W. Role of protease activated receptor 1 and 2 signaling in hypoxia-induced angiogenesis. Arterioscler Thromb Vasc Biol. 2007;27:1456-62 pubmed
    ..The TF-VIIa complex also directly cleaves PAR2 and promotes angiogenesis in vitro in TF cytoplasmic domain-deleted (TF(deltaCT)) mice...
  10. Wang P, Kumar P, Wang C, DeFea K. Differential regulation of class IA phosphoinositide 3-kinase catalytic subunits p110 alpha and beta by protease-activated receptor 2 and beta-arrestins. Biochem J. 2007;408:221-30 pubmed
  11. Shpacovitch V, Feld M, Hollenberg M, Luger T, Steinhoff M. Role of protease-activated receptors in inflammatory responses, innate and adaptive immunity. J Leukoc Biol. 2008;83:1309-22 pubmed publisher
    ..Understanding the mechanisms by which PARs exert the effects of serine proteases on immune cells may lead to new therapeutic strategies in inflammation, immune defense, and allergy. ..
  12. Antoniak S, Rojas M, Spring D, Bullard T, Verrier E, Blaxall B, et al. Protease-activated receptor 2 deficiency reduces cardiac ischemia/reperfusion injury. Arterioscler Thromb Vasc Biol. 2010;30:2136-42 pubmed publisher
    ..PAR-2 deficiency reduces myocardial infarction and heart remodeling after I/R injury. ..
  13. Afkhami Goli A, Noorbakhsh F, Keller A, Vergnolle N, Westaway D, Jhamandas J, et al. Proteinase-activated receptor-2 exerts protective and pathogenic cell type-specific effects in Alzheimer's disease. J Immunol. 2007;179:5493-503 pubmed
    ..We report suppression of proteinase-activated receptor-2 (PAR2) expression in neurons of brains from AD patients, whereas PAR2 expression was increased in proximate glial cells, ..
  14. Kagota S, Chia E, McGuire J. Preserved arterial vasodilatation via endothelial protease-activated receptor-2 in obese type 2 diabetic mice. Br J Pharmacol. 2011;164:358-71 pubmed publisher
    In non-obese diabetic animals, protease-activated receptor-2 (PAR2) agonists are more effective vasodilators, which is attributed to increased COX-2 and endothelial NOS (eNOS) activities...
  15. Roviezzo F, Bucci M, Brancaleone V, Di Lorenzo A, Geppetti P, Farneti S, et al. Proteinase-activated receptor-2 mediates arterial vasodilation in diabetes. Arterioscler Thromb Vasc Biol. 2005;25:2349-54 pubmed
    ..Here, using nonobese diabetic (NOD) mice at different disease stages, we have evaluated the role of PAR2 in the arterial vascular response during diabetes progression...
  16. Schmidlin F, Amadesi S, Dabbagh K, Lewis D, Knott P, Bunnett N, et al. Protease-activated receptor 2 mediates eosinophil infiltration and hyperreactivity in allergic inflammation of the airway. J Immunol. 2002;169:5315-21 pubmed
    ..epithelial cells, myocytes, and nerve fibers of the respiratory tract by cleaving proteinase-activated receptor 2 (PAR2)...
  17. Cenac N, Coelho A, Nguyen C, Compton S, Andrade Gordon P, MacNaughton W, et al. Induction of intestinal inflammation in mouse by activation of proteinase-activated receptor-2. Am J Pathol. 2002;161:1903-15 pubmed
    ..Because trypsin and tryptase are found at high levels in the colon lumen of patients with Crohn's disease or ulcerative colitis, our data may bear directly on the pathophysiology of human inflammatory bowel diseases. ..
  18. Liang G, Barker T, Xie Z, Charles N, Rivera J, Druey K. Naive T cells sense the cysteine protease allergen papain through protease-activated receptor 2 and propel TH2 immunity. J Allergy Clin Immunol. 2012;129:1377-1386.e13 pubmed publisher
    ..Papain-triggered innate immune responses were dependent on both CD4 T cells and PAR2 and were strongly reduced in the absence of CCR4, the primary receptor for CCL17/CCL22...
  19. Moffatt J, Jeffrey K, Cocks T. Protease-activated receptor-2 activating peptide SLIGRL inhibits bacterial lipopolysaccharide-induced recruitment of polymorphonuclear leukocytes into the airways of mice. Am J Respir Cell Mol Biol. 2002;26:680-4 pubmed
    Protease-activated receptor-2 (PAR2) acts as a receptor for trypsin and trypsin-like enzymes. The role of this receptor in airway inflammation is uncertain...
  20. 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
    ..We report on the effects of instilling PAR-activating peptides (PAR-APs, including PAR1-, PAR2-, and PAR4-AP) into the lungs of ventilated or spontaneously breathing mice...
  21. Briot A, Lacroix M, Robin A, Steinhoff M, Deraison C, Hovnanian A. Par2 inactivation inhibits early production of TSLP, but not cutaneous inflammation, in Netherton syndrome adult mouse model. J Invest Dermatol. 2010;130:2736-42 pubmed publisher
    ..initiated by unrestricted kallikrein 5 (KLK5) activity, which directly activates proteinase-activated receptor 2 (PAR2)-mediated expression of TSLP and favors a cutaneous proallergic microenvironment independently of the environment ..
  22. Ferrell W, Lockhart J, Kelso E, Dunning L, Plevin R, Meek S, et al. Essential role for proteinase-activated receptor-2 in arthritis. J Clin Invest. 2003;111:35-41 pubmed
  23. 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. ..
  24. 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. ..
  25. Ahamed J, Niessen F, Kurokawa T, Lee Y, Bhattacharjee G, Morrissey J, et al. Regulation of macrophage procoagulant responses by the tissue factor cytoplasmic domain in endotoxemia. Blood. 2007;109:5251-9 pubmed
    ..Increased TF expression of TF(Delta CT) macrophages does not require PAR2 and is specific for toll-like receptor, but not interferon gamma receptor, signaling...
  26. Kunzelmann K, Sun J, Markovich D, König J, Mürle B, Mall M, et al. Control of ion transport in mammalian airways by protease activated receptors type 2 (PAR-2). FASEB J. 2005;19:969-70 pubmed
  27. Arizmendi N, Abel M, Mihara K, Davidson C, Polley D, Nadeem A, et al. Mucosal allergic sensitization to cockroach allergens is dependent on proteinase activity and proteinase-activated receptor-2 activation. J Immunol. 2011;186:3164-72 pubmed publisher
    ..We conclude that CE induces PAR(2)-dependent allergic airway sensitization in a mouse model of allergic airway inflammation. PAR(2) activation may be a general mechanism used by aeroallergens to induce allergic sensitization...
  28. 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. ..
  29. Camerer E, Barker A, Duong D, Ganesan R, Kataoka H, Cornelissen I, et al. Local protease signaling contributes to neural tube closure in the mouse embryo. Dev Cell. 2010;18:25-38 pubmed publisher
    ..Par1 and Par2 were expressed in surface ectoderm, and Par2 was expressed selectively along the line of closure...
  30. Redecha P, Franzke C, Ruf W, Mackman N, Girardi G. Neutrophil activation by the tissue factor/Factor VIIa/PAR2 axis mediates fetal death in a mouse model of antiphospholipid syndrome. J Clin Invest. 2008;118:3453-61 pubmed publisher
    ..Neutrophils from aPL-treated mice expressed protease-activated receptor 2 (PAR2), and stimulation of this receptor led to neutrophil activation, trophoblast injury, and fetal death...
  31. Briot A, Deraison C, Lacroix M, Bonnart C, Robin A, Besson C, et al. Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome. J Exp Med. 2009;206:1135-47 pubmed publisher
    ..They illustrate the crucial role of protease signaling in skin inflammation and point to new therapeutic targets for NS as well as candidate genes for AD and atopy. ..
  32. Fields R, Schoenecker J, Hart J, Hoffman M, Pizzo S, Lawson J. Protease-activated receptor-2 signaling triggers dendritic cell development. Am J Pathol. 2003;162:1817-22 pubmed
    ..These results suggest that endogenous serine proteases stimulate DC development in vitro. Thus, serine proteases may help trigger adaptive immune responses in vivo. ..
  33. Szabo R, Uzzun Sales K, Kosa P, Shylo N, Godiksen S, Hansen K, et al. Reduced prostasin (CAP1/PRSS8) activity eliminates HAI-1 and HAI-2 deficiency-associated developmental defects by preventing matriptase activation. PLoS Genet. 2012;8:e1002937 pubmed publisher
  34. Ramelli G, Fuertes S, Narayan S, Busso N, Acha Orbea H, So A. Protease-activated receptor 2 signalling promotes dendritic cell antigen transport and T-cell activation in vivo. Immunology. 2010;129:20-7 pubmed publisher
    Deficiency of protease-activated receptor-2 (PAR2) modulates inflammation in several models of inflammatory and autoimmune disease, although the underlying mechanism(s) are not understood...
  35. Hara K, Iijima K, Elias M, Seno S, Tojima I, Kobayashi T, et al. Airway uric acid is a sensor of inhaled protease allergens and initiates type 2 immune responses in respiratory mucosa. J Immunol. 2014;192:4032-42 pubmed publisher
    ..These findings provide mechanistic insights into the development of type 2 immunity to airborne allergens and recognize airway UA as a key player that regulates the process in respiratory mucosa. ..
  36. Hyun E, Ramachandran R, Cenac N, Houle S, Rousset P, Saxena A, et al. Insulin modulates protease-activated receptor 2 signaling: implications for the innate immune response. J Immunol. 2010;184:2702-9 pubmed publisher
    ..Our data point to an anti-inflammatory action of insulin that targets the acute innate inflammatory response triggered by PAR(2). ..
  37. D Andrea M, Saban M, Nguyen N, Andrade Gordon P, Saban R. Expression of protease-activated receptor-1, -2, -3, and -4 in control and experimentally inflamed mouse bladder. Am J Pathol. 2003;162:907-23 pubmed
    ..It is timely to understand the role of tryptase signaling and PARs in the context of bladder biology. ..
  38. Sipe W, Brierley S, Martin C, Phillis B, Cruz F, Grady E, et al. Transient receptor potential vanilloid 4 mediates protease activated receptor 2-induced sensitization of colonic afferent nerves and visceral hyperalgesia. Am J Physiol Gastrointest Liver Physiol. 2008;294:G1288-98 pubmed publisher
    ..These responses require the presence of functional TRPV4. Therefore, TRPV4 is required for PAR(2)-induced mechanical hyperalgesia and excitation of colonic afferent neurons. ..
  39. Moraes T, Martin R, Plumb J, Vachon E, Cameron C, Danesh A, et al. Role of PAR2 in murine pulmonary pseudomonal infection. Am J Physiol Lung Cell Mol Physiol. 2008;294:L368-77 pubmed
    ..by various mechanisms, including via cleavage and activation of protease-activated receptors (PAR) such as PAR2. In addition, proteinases such as neutrophil and/or Pseudomonas-derived elastase can disarm PAR2 resulting in loss ..
  40. Sherwood C, Daines M, Price T, Vagner J, Boitano S. A highly potent agonist to protease-activated receptor-2 reveals apical activation of the airway epithelium resulting in Ca2+-regulated ion conductance. Am J Physiol Cell Physiol. 2014;307:C718-26 pubmed publisher
    ..Protease-activated receptor-2 (PAR2) is expressed both apically and basolaterally throughout the airway epithelium...
  41. Hansen K, Sherman P, Cellars L, Andrade Gordon P, Pan Z, Baruch A, et al. A major role for proteolytic activity and proteinase-activated receptor-2 in the pathogenesis of infectious colitis. Proc Natl Acad Sci U S A. 2005;102:8363-8 pubmed
    ..not from sham-infected mice, contains active serine proteinases that can activate proteinase-activated receptor-2 (PAR2). We have identified granzyme A and murine trypsins to be present in C...
  42. Wang J, Chakrabarty S, Bui Q, Ruf W, Samad F. Hematopoietic tissue factor-protease-activated receptor 2 signaling promotes hepatic inflammation and contributes to pathways of gluconeogenesis and steatosis in obese mice. Am J Pathol. 2015;185:524-35 pubmed publisher
    ..in high-fat diet-fed mice that lack the cytoplasmic domain of TF (F3) (TF(ΔCT)) or that are deficient in PAR2 (F2rl1), as well as by pharmacological inhibition of TF-PAR2 signaling in diet-induced obese mice...
  43. Yoon H, Radulovic M, Drucker K, Wu J, Scarisbrick I. The thrombin receptor is a critical extracellular switch controlling myelination. Glia. 2015;63:846-59 pubmed publisher
    ..These studies identify the thrombin receptor as a powerful extracellular regulatory switch that could be readily targeted to improve myelin production in the face of white matter injury and disease. ..
  44. Burda J, Radulovic M, Yoon H, Scarisbrick I. Critical role for PAR1 in kallikrein 6-mediated oligodendrogliopathy. Glia. 2013;61:1456-70 pubmed publisher
  45. Michael E, Kuliopulos A, Covic L, Steer M, Perides G. Pharmacological inhibition of PAR2 with the pepducin P2pal-18S protects mice against acute experimental biliary pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2013;304:G516-26 pubmed publisher
    Pancreatic acinar cells express proteinase-activated receptor-2 (PAR2) that is activated by trypsin-like serine proteases and has been shown to exert model-specific effects on the severity of experimental pancreatitis, i.e...
  46. Tudpor K, van der Eerden B, Jongwattanapisan P, Roelofs J, van Leeuwen J, Bindels R, et al. Thrombin receptor deficiency leads to a high bone mass phenotype by decreasing the RANKL/OPG ratio. Bone. 2015;72:14-22 pubmed publisher
    ..Consequently, TR deficiency inhibits osteoclastogenesis, resulting in a high bone mass phenotype. ..
  47. Kawaguchi M, Kanemaru A, Sawaguchi A, Yamamoto K, Baba T, Lin C, et al. Hepatocyte growth factor activator inhibitor type 1 maintains the assembly of keratin into desmosomes in keratinocytes by regulating protease-activated receptor 2-dependent p38 signaling. Am J Pathol. 2015;185:1610-23 pubmed publisher
    ..These results suggest that HAI-1 may have a critical role in maintaining normal keratinocyte morphology through regulation of PAR-2-dependent p38 mitogen-activated protein kinase signaling. ..
  48. Versteeg H, Schaffner F, Kerver M, Ellies L, Andrade Gordon P, Mueller B, et al. Protease-activated receptor (PAR) 2, but not PAR1, signaling promotes the development of mammary adenocarcinoma in polyoma middle T mice. Cancer Res. 2008;68:7219-27 pubmed publisher
    ..To address the contributions of PAR1 and PAR2 to breast cancer development, we established cohorts of mouse mammary tumor virus-polyoma middle T (PyMT) PAR1(-/-) ..
  49. Cattaruzza F, Lyo V, Jones E, Pham D, Hawkins J, Kirkwood K, et al. Cathepsin S is activated during colitis and causes visceral hyperalgesia by a PAR2-dependent mechanism in mice. Gastroenterology. 2011;141:1864-74.e1-3 pubmed publisher
    ..Macrophage cathepsins are activated during colitis, and Cat-S activates nociceptors to induce visceral pain via protease-activated receptor-2. Cat-S mediates colitis pain and is a potential therapeutic target. ..
  50. De Cunto G, Cardini S, Cirino G, Geppetti P, Lungarella G, Lucattelli M. Pulmonary hypertension in smoking mice over-expressing protease-activated receptor-2. Eur Respir J. 2011;37:823-34 pubmed publisher
    ..PAR-2 signalling can influence the production and release of many factors, which may play a role in the development of PH in smokers. ..
  51. Kawagoe J, Takizawa T, Matsumoto J, Tamiya M, Meek S, Smith A, et al. Effect of protease-activated receptor-2 deficiency on allergic dermatitis in the mouse ear. Jpn J Pharmacol. 2002;88:77-84 pubmed
    ..The vascular permeability in the ears after PCA was not different between WT and PAR-2(-/-) mice. These results strongly suggest that PAR-2 plays a crucial role in type IV allergic dermatitis but not in type I allergic dermatitis. ..
  52. Julovi S, Xue M, Dervish S, Sambrook P, March L, Jackson C. Protease activated receptor-2 mediates activated protein C-induced cutaneous wound healing via inhibition of p38. Am J Pathol. 2011;179:2233-42 pubmed publisher
    ..In summary, although APC acts through both PAR-1 and PAR-2 to activate Akt and to increase keratinocyte proliferation, APC-induced murine wound healing depends on PAR-2 activity and inhibition of P-p38. ..
  53. Gu Q, Lee L. House dust mite potentiates capsaicin-evoked Ca2+ transients in mouse pulmonary sensory neurons via activation of protease-activated receptor-2. Exp Physiol. 2012;97:534-43 pubmed publisher
  54. Cupit L, Schmidt V, Miller F, Bahou W. Distinct PAR/IQGAP expression patterns during murine development: implications for thrombin-associated cytoskeletal reorganization. Mamm Genome. 2004;15:618-29 pubmed
    ..These data provide a panoramic survey of PAR/ IQGAP expression as an initial approach to dissect thrombin signaling pathways linked to cytoskeletal reorganization. ..
  55. Paszcuk A, Quintão N, Fernandes E, Juliano L, Chapman K, Andrade Gordon P, et al. Mechanisms underlying the nociceptive and inflammatory responses induced by trypsin in the mouse paw. Eur J Pharmacol. 2008;581:204-15 pubmed
    ..These pieces of evidence provide new insights on the role of trypsin in pain and inflammation. ..
  56. Bucci M, Vellecco V, Harrington L, Brancaleone V, Roviezzo F, Mattace Raso G, et al. Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR(2) ) is involved in vascular function. Br J Pharmacol. 2013;168:411-20 pubmed publisher
    ..Cross-talk between PAR(2) and TLR4 contributes to vascular homeostasis. ..
  57. Jackson M, Moradi B, Zaki S, Smith M, McCracken S, Smith S, et al. Depletion of protease-activated receptor 2 but not protease-activated receptor 1 may confer protection against osteoarthritis in mice through extracartilaginous mechanisms. Arthritis Rheumatol. 2014;66:3337-48 pubmed publisher
  58. Matos N, Silva J, Damasceno K, Cassali G, Lemos V, Duarte I, et al. Proteinase-activated receptor 2 blockade impairs CCL11- or allergen-induced eosinophil recruitment in experimental pleurisy. Eur J Pharmacol. 2014;740:627-33 pubmed publisher
    ..Taken together, our results suggest that PAR-2 activation through endogenous MC tryptase activity could be required, at least partially, to mediate CCL11-induced eosinophil migration. ..
  59. Frateschi S, Camerer E, Crisante G, Rieser S, Membrez M, Charles R, et al. PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin. Nat Commun. 2011;2:161 pubmed
    ..that transgenic expression in mouse skin of either CAP1/Prss8 (K14-CAP1/Prss8) or protease-activated receptor-2 (PAR2; Grhl3(PAR2/+)), one candidate downstream target, causes epidermal hyperplasia, ichthyosis and itching...
  60. Akiyama T, Tominaga M, Davoodi A, Nagamine M, Blansit K, Horwitz A, et al. Cross-sensitization of histamine-independent itch in mouse primary sensory neurons. Neuroscience. 2012;226:305-12 pubmed publisher
    ..PAR-2 expressed in pruriceptive nerve endings is a potential target to reduce sensitization associated with chronic itch...
  61. Terada Y, Fujimura M, Nishimura S, Tsubota M, Sekiguchi F, Nishikawa H, et al. Contribution of TRPA1 as a downstream signal of proteinase-activated receptor-2 to pancreatic pain. J Pharmacol Sci. 2013;123:284-7 pubmed
    ..if TRPA1, like TRPV1, contributes to pancreatic nociceptor excitation following proteinase-activated receptor-2 (PAR2) stimulation and to pancreatitis-related pain in mice...
  62. Grant A, Cottrell G, Amadesi S, Trevisani M, Nicoletti P, Materazzi S, et al. Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice. J Physiol. 2007;578:715-33 pubmed
    ..Proteases that are generated during inflammation and disease cleave protease-activated receptor 2 (PAR2) on afferent nerves to cause mechanical hyperalgesia in the skin and intestine by unknown mechanisms...
  63. 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. ..
  64. Kopec A, Abrahams S, Thornton S, Palumbo J, Mullins E, Divanovic S, et al. Thrombin promotes diet-induced obesity through fibrin-driven inflammation. J Clin Invest. 2017;127:3152-3166 pubmed publisher
    ..Collectively, these data provide proof of concept that targeting thrombin or fibrin(ogen) may limit pathologies in obese patients. ..
  65. Park Y, Yang J, Zhang H, Chen X, Zhang C. Effect of PAR2 in regulating TNF-? and NAD(P)H oxidase in coronary arterioles in type 2 diabetic mice. Basic Res Cardiol. 2011;106:111-23 pubmed publisher
    Protease-activated receptor-2 (PAR2) is expressed in endothelial cells and mediates endothelium-dependent vasodilation...
  66. Wilson B, Harada R, Leduy L, Hollenberg M, Nepveu A. CUX1 transcription factor is a downstream effector of the proteinase-activated receptor 2 (PAR2). J Biol Chem. 2009;284:36-45 pubmed publisher
    ..Here we show that the CUX1 homeodomain protein is a downstream effector of PAR2. Treatment of epithelial and fibroblastic cells with trypsin or the PAR2-activating peptide (PAR2-AP) caused a ..
  67. Sandberg W, Halvorsen B, Yndestad A, Smith C, Otterdal K, Brosstad F, et al. Inflammatory interaction between LIGHT and proteinase-activated receptor-2 in endothelial cells: potential role in atherogenesis. Circ Res. 2009;104:60-8 pubmed publisher
    ..Our findings suggest that LIGHT/PAR-2-driven inflammation could be a pathogenic loop in atherogenesis potentially representing a target for therapy in this disorder. ..
  68. Su X, Matthay M. Role of protease activated receptor 2 in experimental acute lung injury and lung fibrosis. Anat Rec (Hoboken). 2009;292:580-6 pubmed publisher
    b>Protease activated receptor 2 (PAR2) is widely-distributed (lung, liver, kidney, etc.) and expressed by variety of cells (i.e. leukocytes, epithelial cells, endothelial cells, and fibroblast)...
  69. Maharshak N, Huh E, Paiboonrungruang C, Shanahan M, Thurlow L, Herzog J, et al. Enterococcus faecalis Gelatinase Mediates Intestinal Permeability via Protease-Activated Receptor 2. Infect Immun. 2015;83:2762-70 pubmed publisher
    ..faecalis strains indicated paracellular permeability. A protease-activated receptor 2 (PAR2) antagonist and PAR2-deficient (PAR2(-/-)) mice were used to investigate the role of this receptor in E...
  70. Tan M, Yan H, Li J, Li W, Fu Y, Chen W, et al. Thrombin Stimulated Platelet-Derived Exosomes Inhibit Platelet-Derived Growth Factor Receptor-Beta Expression in Vascular Smooth Muscle Cells. Cell Physiol Biochem. 2016;38:2348-65 pubmed publisher
    ..Our data indicate that activated platelet-derived exosomes containing miR-223, miR-339 and miR-21 could be transferred into SMCs and inhibit PDGFR? expression; these exosomal miRNAs may be a biomarker for predicting atherothrombosis. ..