Ptger4

Summary

Gene Symbol: Ptger4
Description: prostaglandin E receptor 4 (subtype EP4)
Alias: EP4, Ptgerep4, PGE receptor EP4 subtype, PGE2 receptor EP4 subtype, prostaglandin E receptor 4 (EP4 subtype), prostaglandin E receptor EP4 subtype, prostaglandin E2 receptor EP4 subtype, prostanoid EP4 receptor
Species: mouse

Top Publications

  1. ncbi Induction of adherent activity in mastocytoma P-815 cells by the cooperation of two prostaglandin E2 receptor subtypes, EP3 and EP4
    Noriyuki Hatae
    Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo ku, Kyoto 606, Japan
    J Biol Chem 278:17977-81. 2003
  2. ncbi Significance and therapeutic potential of prostaglandin E2 receptor in hepatic ischemia/reperfusion injury in mice
    Yukiyasu Kuzumoto
    Department of Surgery, Nara Medical University, Nara, Japan
    Hepatology 42:608-17. 2005
  3. ncbi Antagonism of the prostaglandin E receptor EP4 inhibits metastasis and enhances NK function
    Namita Kundu
    Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Breast Cancer Res Treat 117:235-42. 2009
  4. ncbi Failure of postnatal ductus arteriosus closure in prostaglandin transporter-deficient mice
    Hee Yoon Chang
    Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Circulation 121:529-36. 2010
  5. ncbi The role of prostaglandin E2 receptors in the pathogenesis of rheumatoid arthritis
    Jennifer M McCoy
    Pfizer Global Research and Development, Department of Inflammation and Pathology, Groton, Connecticut 06340, USA
    J Clin Invest 110:651-8. 2002
  6. ncbi Patent ductus arteriosus and neonatal death in prostaglandin receptor EP4-deficient mice
    E Segi
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan
    Biochem Biophys Res Commun 246:7-12. 1998
  7. ncbi Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3
    F Ushikubi
    Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan
    Nature 395:281-4. 1998
  8. ncbi Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3
    Tomonori Kunikata
    Department of Pharmacology and Faculty of Medicine and Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606 8501, Japan
    Nat Immunol 6:524-31. 2005
  9. ncbi The prostaglandin receptor EP4 triggers remodelling of the cardiovascular system at birth
    M Nguyen
    Department of Medicine, University of North Carolina at Chapel Hill, 27599 7248, USA
    Nature 390:78-81. 1997
  10. ncbi Prostanoid receptors: structures, properties, and functions
    S Narumiya
    Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto, Japan
    Physiol Rev 79:1193-226. 1999

Scientific Experts

  • Wissam H Faour
  • Karin Muller-Decker
  • X Julia Xu
  • Li Yang
  • Keisuke Nakagawa
  • Kenji Kabashima
  • Hua Zhu Ke
  • Vladimir R Babaev
  • M Li
  • Niklas Kern
  • William L Smith
  • Kotha Subbaramaiah
  • Ambra Pozzi
  • F Schweda
  • Chris R J Kennedy
  • Gunther Zahner
  • M P Akhter
  • Shuh Narumiya
  • Yukihiko Sugimoto
  • Kousaku Ohinata
  • Y Sugimoto
  • S Narumiya
  • Koji Takayama
  • Chengcan Yao
  • Akiyoshi Hara
  • Takayuki Fujino
  • Chao Xie
  • Fumitaka Ushikubi
  • Katsuhiro Ono
  • Matthew D Breyer
  • Toshiyuki Matsuoka
  • Atsushi Ichikawa
  • A Ichikawa
  • F Ushikubi
  • T Nomi
  • Lawrence G Raisz
  • Carol C Pilbeam
  • Koh Ichi Yuhki
  • Koh-ichi Yuhki
  • Osamu Takahata
  • Shuhko Kuriyama
  • Takehiro Yamada
  • MyTrang Nguyen
  • Chihiro Suzuki
  • Angus Stock
  • Michelle M Duffy
  • Kitipong Soontrapa
  • Hee Yoon Chang
  • Hiroshi Katoh
  • Erin M Stitt-Cavanagh
  • Daiji Sakata
  • Pamela Harding
  • REGIS J O'KEEFE
  • Namita Kundu
  • Qi Gao
  • R Hori
  • Xinping Zhang
  • Edward M Schwarz
  • Katia Boniface
  • Ryosuke Tsutsumi
  • H Kataoka
  • Masataka Majima
  • Chuanming Hao
  • Manabu Minami
  • Jernej Murn
  • Tomoyuki Furuyashiki
  • Ryo Hatazawa
  • Masaaki Yoshikawa
  • X Wu
  • H Oka
  • Rania Nasrallah
  • Reena Rao
  • Yoko Fujiwara
  • Darshini B Trivedi
  • Emi Kamoshita
  • M Sho
  • H Kanehiro
  • Y Nakajima
  • Sherven Sharma
  • Hideji Karibe
  • Y Kuzumoto
  • Yasuhiro Kobayashi
  • Yuji Okada
  • Tomonori Kunikata
  • Rolf M Nusing
  • Yukiyasu Kuzumoto
  • T M Coffman
  • Takanobu Taniguchi
  • B H Koller
  • Louis C Martineau

Detail Information

Publications78

  1. ncbi Induction of adherent activity in mastocytoma P-815 cells by the cooperation of two prostaglandin E2 receptor subtypes, EP3 and EP4
    Noriyuki Hatae
    Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo ku, Kyoto 606, Japan
    J Biol Chem 278:17977-81. 2003
    ..Consistent with mRNA expression of the G(s)-coupled EP4- and G(i)-coupled EP3-PGE receptor subtypes, P-815 cell adhesion was accelerated by treatment with a selective EP4 ..
  2. ncbi Significance and therapeutic potential of prostaglandin E2 receptor in hepatic ischemia/reperfusion injury in mice
    Yukiyasu Kuzumoto
    Department of Surgery, Nara Medical University, Nara, Japan
    Hepatology 42:608-17. 2005
    Prostaglandin E2 (PGE2) mediates a variety of innate and adaptive immunity through four distinct receptors: EP1-EP4. It has been suggested that each EP plays a unique and pivotal role in various disease conditions...
  3. ncbi Antagonism of the prostaglandin E receptor EP4 inhibits metastasis and enhances NK function
    Namita Kundu
    Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Breast Cancer Res Treat 117:235-42. 2009
    ..Malignant and immortalized normal mammary epithelial cell lines express all four EP. The EP4 antagonist AH23848 reduced the ability of tumor cells to colonize the lungs or to spontaneously metastasize from ..
  4. ncbi Failure of postnatal ductus arteriosus closure in prostaglandin transporter-deficient mice
    Hee Yoon Chang
    Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Circulation 121:529-36. 2010
    ..The rate-limiting step in PGE(2) signal termination is PGE(2) uptake by the transporter PGT...
  5. ncbi The role of prostaglandin E2 receptors in the pathogenesis of rheumatoid arthritis
    Jennifer M McCoy
    Pfizer Global Research and Development, Department of Inflammation and Pathology, Groton, Connecticut 06340, USA
    J Clin Invest 110:651-8. 2002
    ..Homozygous deletion of the EP1, EP2, or EP3 receptors did not affect the development of arthritis, whereas EP4 receptor-deficient mice showed decreased incidence and severity of disease...
  6. ncbi Patent ductus arteriosus and neonatal death in prostaglandin receptor EP4-deficient mice
    E Segi
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan
    Biochem Biophys Res Commun 246:7-12. 1998
    The physiological role of the prostaglandin E2 receptor EP4 subtype was investigated by generation of EP4-deficient-mice by gene targeting...
  7. ncbi Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3
    F Ushikubi
    Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan
    Nature 395:281-4. 1998
    ..PGE2 acts by interacting with four subtypes of PGE receptor, the EP1, EP2, EP3 and EP4 receptors. Here we generate mice lacking each of these receptors by homologous recombination...
  8. ncbi Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3
    Tomonori Kunikata
    Department of Pharmacology and Faculty of Medicine and Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606 8501, Japan
    Nat Immunol 6:524-31. 2005
    ..Thus, the PGE(2)-EP3 pathway is an important negative modulator of allergic reactions...
  9. ncbi The prostaglandin receptor EP4 triggers remodelling of the cardiovascular system at birth
    M Nguyen
    Department of Medicine, University of North Carolina at Chapel Hill, 27599 7248, USA
    Nature 390:78-81. 1997
    ..This requirement is absent in mice lacking the prostaglandin E2 EP4 receptor (EP4(-/-) mice)...
  10. ncbi Prostanoid receptors: structures, properties, and functions
    S Narumiya
    Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto, Japan
    Physiol Rev 79:1193-226. 1999
    ..In this article, we summarize these findings and attempt to give an overview of the current status of research on the prostanoid receptors...
  11. ncbi Prostaglandin E receptor subtype EP4 agonist protects cochleae against noise-induced trauma
    R Hori
    Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kawaharacho 54, Shogoin, Sakyo ku, Kyoto, Japan
    Neuroscience 160:813-9. 2009
    ..by the prostanoid receptors prostaglandin I receptor and the prostaglandin E receptor subtypes EP1, EP2, EP3, and EP4, the respective agonists for which have been purified...
  12. ncbi The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut
    Kenji Kabashima
    Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto, Japan
    J Clin Invest 109:883-93. 2002
    ..Among the prostanoid receptor-deficient mice, only EP4-deficient mice and not mice deficient in either DP, EP1, EP2, EP3, FP, IP, or TP developed severe colitis with 3% ..
  13. ncbi Prostaglandin E2-EP4 signaling initiates skin immune responses by promoting migration and maturation of Langerhans cells
    Kenji Kabashima
    Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606 8501, Japan
    Nat Med 9:744-9. 2003
    ..all four PGE receptor subtypes, their migration to regional lymph nodes was decreased only in EP4-deficient (Ptger4-/-) mice and in wild-type mice treated with an EP4 antagonist...
  14. ncbi Impaired adrenocorticotropic hormone response to bacterial endotoxin in mice deficient in prostaglandin E receptor EP1 and EP3 subtypes
    Yoko Matsuoka
    Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 100:4132-7. 2003
    ..By using mice lacking each of the four PGE receptors (EP1-EP4) and an EP1-selective antagonist, ONO-8713, we showed that both EP1 and EP3 are required for adrenocorticotropic ..
  15. ncbi Activation of prostaglandin E receptor EP4 subtype suppresses food intake in mice
    Kousaku Ohinata
    Division of Food Bioscience and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto 611 0011, Japan
    Prostaglandins Other Lipid Mediat 81:31-6. 2006
    ..We examined which of four distinct subtypes of PGE2 receptors (EP1-EP4) mediated the anorexigenic action of PGE2 using highly selective ligands. PGE2 at a dose of 0...
  16. ncbi PGE(2) induces COX-2 expression in podocytes via the EP(4) receptor through a PKA-independent mechanism
    Wissam H Faour
    Kidney Research Centre, Division of Nephrology, Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada K1H 8M5
    Cell Signal 20:2156-64. 2008
    ..This PGE(2)-induced signaling network activated by increased P(gc) could be detrimental to podocyte health and glomerular filtration barrier integrity...
  17. ncbi Prostaglandin E receptor type 4-associated protein interacts directly with NF-kappaB1 and attenuates macrophage activation
    Manabu Minami
    Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    J Biol Chem 283:9692-703. 2008
    ..Through the receptor EP4, prostaglandin E(2) (PGE(2)) exerts an anti-inflammatory action in macrophages, suppressing stimulus-induced ..
  18. ncbi Age-induced reprogramming of mast cell degranulation
    MyTrang Nguyen
    Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA
    J Immunol 175:5701-7. 2005
    ..Therefore, elevated PGE2 levels might provide an important pathway by which mast cells are engaged to participate in inflammatory responses in the elderly patient...
  19. ncbi EP2 and EP4 receptors regulate aromatase expression in human adipocytes and breast cancer cells. Evidence of a BRCA1 and p300 exchange
    Kotha Subbaramaiah
    Department of Medicine, Weill Cornell Medical College, New York, New York 10065, USA
    J Biol Chem 283:3433-44. 2008
    ..Reciprocal changes in the interaction between BRCA1, p300, and the aromatase promoter I.3/II contributed to the inductive effects of PGE(2)...
  20. ncbi Bone biomechanical properties in EP4 knockout mice
    M P Akhter
    Osteoporosis Research Center, Creighton University, Omaha, NE, USA
    Calcif Tissue Int 78:357-62. 2006
    ..Despite similar bone size, the absence of an EP(4) receptor may have removed a necessary link for bone adaptation pathways, which resulted in relatively weaker bone properties...
  21. ncbi PGE2 activates cementoclastogenesis by cementoblasts via EP4
    H Oka
    Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical Sciences, Hiroshima University, 1 2 3 Kasumi, Minami Ku, Hiroshima 734 8553, Japan
    J Dent Res 86:974-9. 2007
    ..PGE(2) (100 ng/mL) and EP4 agonist (1 microM) up-regulated RANKL and IL-6 mRNA levels, while they down-regulated OPG mRNA expression...
  22. ncbi Prostaglandin E2 EP4 agonist (ONO-4819) accelerates BMP-induced osteoblastic differentiation
    Keisuke Nakagawa
    Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Asahimachi 1 4 3, Osaka 545 8585, Japan
    Bone 41:543-8. 2007
    ..For this purpose, we have examined ONO-4819, which is a prostaglandin (PG) E2 EP4 receptor selective agonist (EP4A), as a positive modulators for the efficacy of BMPs...
  23. ncbi Activation of PKA and phosphorylation of sodium-dependent vitamin C transporter 2 by prostaglandin E2 promote osteoblast-like differentiation in MC3T3-E1 cells
    X Wu
    Zhejiang Respiratory Drugs Research Laboratory of State Foods and Drugs Administration of China, Medical School of Zhejiang University, No 388 Yuhangtang Road, Hangzhou 310058, China
    Cell Death Differ 14:1792-801. 2007
    ..PGE2-induced plasma membrane translocation of cytoplasm SVCT2, and this effect was abolished by pretreatment with EP4 receptor antagonist, AH-23848B or cAMP-dependent protein kinase A (PKA) inhibitor, H-89...
  24. ncbi Prostaglandin E2-EP4 receptor promotes endothelial cell migration via ERK activation and angiogenesis in vivo
    Reena Rao
    Department of Medicine, Division of Nephrology, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 282:16959-68. 2007
    ..The present study examined the role of the EP4 receptor in regulating endothelial cell proliferation, migration, and tubulogenesis...
  25. ncbi Renal prostaglandin E2 receptor (EP) expression profile is altered in streptozotocin and B6-Ins2Akita type I diabetic mice
    Rania Nasrallah
    Department of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    Am J Physiol Renal Physiol 292:F278-84. 2007
    ..Therefore, knowing the pattern of change in relative EP receptor expression in the kidney could be useful in identifying specific EP targets for the prevention of various components of diabetic kidney disease...
  26. ncbi Attenuated cyclooxygenase-2 expression contributes to patent ductus arteriosus in preterm mice
    Darshini B Trivedi
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536, USA
    Pediatr Res 60:669-74. 2006
    ..Additionally, COX-2 expression was significantly attenuated in the DA of mice deficient in the prostanoid receptor EP4, which also show a patent DA phenotype, suggesting the importance of this receptor for the induction of COX-2 ..
  27. ncbi Prostaglandin E2 is required for ultraviolet B-induced skin inflammation via EP2 and EP4 receptors
    Kenji Kabashima
    Department of Pharmacology, Kyoto University Graduate School of Medicine, Sakyo, Kyoto, Japan
    Lab Invest 87:49-55. 2007
    ..The UV-induced ear swelling at 48 h after exposure was significantly reduced in EP2(-/-), EP4(-/-) or wild-type mice treated with the EP4 antagonist compared to control mice...
  28. ncbi Mesenchymal stem cell inhibition of T-helper 17 cell- differentiation is triggered by cell-cell contact and mediated by prostaglandin E2 via the EP4 receptor
    Michelle M Duffy
    Regenerative Medicine Institute, National Centre for Biomedical Engineering Science and School of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Galway, Ireland
    Eur J Immunol 41:2840-51. 2011
    ..MSC-mediated Th17 inhibition was reversed by a selective EP4 antagonist and was mimicked by synthetic PGE2 and a selective EP4 agonist...
  29. ncbi Central PGE2 exhibits anxiolytic-like activity via EP1 and EP4 receptors in a manner dependent on serotonin 5-HT1A, dopamine D1 and GABAA receptors
    Chihiro Suzuki
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan
    FEBS Lett 585:2357-62. 2011
    ..Taken together, PGE(2) exhibits anxiolytic-like activity via EP(1) and EP(4) receptors, with downstream involvement of 5-HT(1A), D(1) and GABA(A) receptor systems...
  30. ncbi Prostaglandin E2-prostaglandin E receptor subtype 4 (EP4) signaling mediates UV irradiation-induced systemic immunosuppression
    Kitipong Soontrapa
    Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 108:6668-73. 2011
    ..Mice treated with an antagonist for prostaglandin E receptor subtype 4 (EP4), but not those deficient in other prostanoid receptors, show impaired UV-induced immunosuppression, whereas ..
  31. ncbi Prostaglandin E2 suppresses the differentiation of retinoic acid-producing dendritic cells in mice and humans
    Angus Stock
    Medical Research Council Human Immunology Unit, Nuffield Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, England, UK
    J Exp Med 208:761-73. 2011
    ..Given the role of PGE2 in regulating the development of RA-producing DCs, modulating this pathway may prove a novel means to control the development of gut-tropic immune responses...
  32. ncbi A maladaptive role for EP4 receptors in podocytes
    Erin M Stitt-Cavanagh
    Kidney Research Centre, Division of Nephrology, Department of Medicine, Ottawa Hospital, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
    J Am Soc Nephrol 21:1678-90. 2010
    ..e., mechanical stretch) along with prostaglandin E(2) stimulation of its EP4 receptor induced cyclooxygenase-2 in a p38-dependent manner...
  33. ncbi COX-2 and prostaglandin EP3/EP4 signaling regulate the tumor stromal proangiogenic microenvironment via CXCL12-CXCR4 chemokine systems
    Hiroshi Katoh
    Department of Pharmacology, Kitasato University, School of Medicine, Kitasato 1 15 1, Sagamihara, Kanagawa, 228 8555, Japan
    Am J Pathol 176:1469-83. 2010
    ..Moreover, stromal formation after tumor implantation was suppressed in EP3-/- mice and EP4-/- mice, in which stromal expression of CXCL12/CXCR4 and S100A4 was reduced...
  34. ncbi Gene expression profiling of dilated cardiomyopathy in older male EP4 knockout mice
    Pamela Harding
    Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan, USA
    Am J Physiol Heart Circ Physiol 298:H623-32. 2010
    Using a line of mice with cardiac-specific knockout (KO) of the EP4 receptor gene, experiments were designed to determine whether a cardiac phenotype developed with age...
  35. ncbi Rescue of impaired fracture healing in COX-2-/- mice via activation of prostaglandin E2 receptor subtype 4
    Chao Xie
    The Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Am J Pathol 175:772-85. 2009
    ..Using prostaglandin E2 receptor (EP)2 and EP4 agonists, we examined the effects of EP receptor activation in compensation for the lack of COX-2 during fracture ..
  36. ncbi Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion
    Chengcan Yao
    Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto, Japan
    Nat Med 15:633-40. 2009
    ..Here we show that prostaglandin E2 (PGE2) acting on its receptor EP4 on T cells and dendritic cells not only facilitates TH1 cell differentiation but also amplifies interleukin-23-..
  37. ncbi PGE2 signaling through the EP4 receptor on fibroblasts upregulates RANKL and stimulates osteolysis
    Ryosuke Tsutsumi
    Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA
    J Bone Miner Res 24:1753-62. 2009
    ..However, the PGE2 receptor (EP1, EP2, or EP4), and cell type in which it is expressed, which is responsible for PGE2 induction of RANKL during wear debris-..
  38. ncbi Effects of global or targeted deletion of the EP4 receptor on the response of osteoblasts to prostaglandin in vitro and on bone histomorphometry in aged mice
    Qi Gao
    New England Musculoskeletal Institute, University of Connecticut Health Center, Farmington, CT 06030, USA
    Bone 45:98-103. 2009
    Because global deletion of the prostaglandin EP4 receptor results in neonatal lethality, we generated a mouse with targeted EP4 receptor deletion using Cre-LoxP methodology and a 2...
  39. ncbi Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling
    Katia Boniface
    Department of Immunology, Schering Plough Biopharma, Palo Alto, CA 94304, USA
    J Exp Med 206:535-48. 2009
    ..In human purified naive T cells, PGE2 acts via prostaglandin receptor EP2- and EP4-mediated signaling and cyclic AMP pathways to up-regulate IL-23 and IL-1 receptor expression...
  40. ncbi Prostaglandin E2 regulates B cell proliferation through a candidate tumor suppressor, Ptger4
    Jernej Murn
    CEA, DSV, Institut de Radiobiologie Cellulaire et Moleculaire, Laboratoire d Exploration Fonctionnelle des Genomes, Evry, France
    J Exp Med 205:3091-103. 2008
    ..Here, we identify Ptger4 as a negative feedback regulator of proliferation in response to BCR signals and show that its encoded EP4 ..
  41. ncbi Augmented cardiac hypertrophy in response to pressure overload in mice lacking the prostaglandin I2 receptor
    Akiyoshi Hara
    Department of Pharmacology, Asahikawa Medical College, Midorigaoka Higashi 2 1 1 1, Asahikawa 078 8510, Japan
    Circulation 112:84-92. 2005
    ..However, their roles in cardiac hypertrophy in vivo remain unknown. We intended to clarify the roles of these receptors in pressure overload-induced cardiac hypertrophy using mice lacking each of their receptors...
  42. ncbi Dominant role of prostaglandin E2 EP4 receptor in furosemide-induced salt-losing tubulopathy: a model for hyperprostaglandin E syndrome/antenatal Bartter syndrome
    Rolf M Nusing
    Institute of Clinical Pharmacology, Johann Wolfgang Goethe University, Theodor Stern Kai 7, Frankfurt 60590, Germany
    J Am Soc Nephrol 16:2354-62. 2005
    ..In wild-type (WT) mice and in mice lacking distinct PGE2 receptors (EP1-/-, EP2-/-, EP3-/-, and EP4-/-), the effect of chronic furosemide administration (7 d) on urine output, sodium and potassium excretion, and ..
  43. ncbi Stimulation of renin release by prostaglandin E2 is mediated by EP2 and EP4 receptors in mouse kidneys
    Frank Schweda
    Institute for Physiology, University of Regensburg, 93042 Regensburg, Germany
    Am J Physiol Renal Physiol 287:F427-33. 2004
    ..In contrast, all four receptor subtypes are involved in the control of renal vascular tone, EP(1) and EP(3) receptors increasing, and EP(2) as well as EP(4) receptors, decreasing it...
  44. ncbi Prostaglandin E2 receptors EP2 and EP4 are up-regulated in peritoneal macrophages and joints of pristane-treated mice and modulate TNF-alpha and IL-6 production
    Jun Akaogi
    University of Florida, P O Box 100221, Gainesville, FL 32610 0221, USA
    J Leukoc Biol 76:227-36. 2004
    ..TNF-alpha mRNA levels also were examined. High levels of EPs (EP4/2>EP1>EP3), iNOS, and COX-2 mRNA were expressed in peritoneal macrophages from pristane-treated but not untreated ..
  45. ncbi p38 MAP kinase mediates mechanically induced COX-2 and PG EP4 receptor expression in podocytes: implications for the actin cytoskeleton
    Louis C Martineau
    Ottawa Health Research Institute, Division of Nephrology, Ottawa Hospital and Univ of Ottawa, 451 Smyth Rd, Rm 1317, Ottawa, Ontario, Canada K1H 8M5
    Am J Physiol Renal Physiol 286:F693-701. 2004
    ..5 Hz) for 2 h. EP4 and COX-2 mRNA increased three- and sevenfold above nonstretched controls, whereas EP1 and COX-1 levels were ..
  46. ncbi Receptors and pathways mediating the effects of prostaglandin E2 on airway tone
    Stephen L Tilley
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, 27599 7248, USA
    Am J Physiol Lung Cell Mol Physiol 284:L599-606. 2003
    ..This segregation of EP receptor function within the airway suggests that PGE(2) analogs that selectively activate the EP2 receptor without activating the EP1/EP3 receptors might prove useful in the treatment of asthma...
  47. ncbi Effects of retinal degeneration and brain size upon spatial reversal learning in mice
    J L Fuller
    Percept Mot Skills 36:947-50. 1973
  48. ncbi Contribution of the two Gs-coupled PGE2-receptors EP2-receptor and EP4-receptor to the inhibition by PGE2 of the LPS-induced TNFalpha-formation in Kupffer cells from EP2-or EP4-receptor-deficient mice. Pivotal role for the EP4-receptor in wild type Kupffe
    Alexandra Fennekohl
    Universitat Potsdam, Institut für Ernährungswissenschaft, Abteilung Biochemie der Ernährung, Arthur Scheunert Allee 114 116, D 14558, Bergholz Rehbrücke, Germany
    J Hepatol 36:328-34. 2002
    ..Four receptor-subtypes have been cloned for PGE2 so far. Two of them, the EP2-receptor and the EP4-receptor are linked to stimulatory Gs-proteins and could mediate the inhibition by PGE2 of TNFalpha-formation.
  49. ncbi Effects of selective prostaglandin EP4 receptor antagonist on osteoclast formation and bone resorption in vitro
    M Tomita
    Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
    Bone 30:159-63. 2002
    ..bone resorption by a cyclic AMP (cAMP)-dependent mechanism that involves prostaglandin E receptors of the EP2 and EP4 subtypes. We tested a potent selective EP4 antagonist (EP4RA), which blocks PGE(2) binding to EP4 receptors...
  50. ncbi Activation of the murine EP3 receptor for PGE2 inhibits cAMP production and promotes platelet aggregation
    J E Fabre
    Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
    J Clin Invest 107:603-10. 2001
    ..The mechanism for this dual action of PGE2 is not clear. This study shows that among the four PGE2 receptors (EP1-EP4), activation of EP3 is sufficient to mediate the proaggregatory actions of low PGE2 concentration...
  51. ncbi Impaired bone resorption to prostaglandin E2 in prostaglandin E receptor EP4-knockout mice
    C Miyaura
    Department of Biochemistry, School of Dentistry, Showa University, 1 5 8 Hatanodai, Shinagawa ku, Tokyo 142 8555, Japan
    J Biol Chem 275:19819-23. 2000
    ..identified PGE receptor subtype(s) mediating this PGE(2) action using mice lacking each subtype (EP1, EP2, EP3, and EP4) of PGE receptor...
  52. ncbi Insight into prostaglandin, leukotriene, and other eicosanoid functions using mice with targeted gene disruptions
    S C Austin
    Center for Experimental Therapeutics, Stellar Chance Labs, University of Pennsylvania, Philadelphia 19104, USA
    Prostaglandins Other Lipid Mediat 58:231-52. 1999
    ..g., receptors for various prostaglandins). This minireview will outline the phenotype of these knockout mice and what has been learned about eicosanoid functions through use of this novel methodology...
  53. ncbi Molecular properties and chromosomal location of cadherin-8
    M Kido
    Doheny Eye Institute, University of Southern California School of Medicine, Los Angeles 90033, USA
    Genomics 48:186-94. 1998
    ..Cadherin-8, as well as cadherin-11, was mapped to a specific region of chromosome 8 that also includes cadherins-1, -3, and -5...
  54. ncbi Prostaglandin E2 receptor subtype EP2 gene expression in the mouse uterus coincides with differentiation of the luminal epithelium for implantation
    H Lim
    Department of Molecular and Integrative Physiology, Ralph L Smith Research Center, University of Kansas Medical Center, Kansas City 66160 7336, USA
    Endocrinology 138:4599-606. 1997
    ..Four major PGE2 receptor subtypes, EP1, EP2, EP3, and EP4, mediate various PGE2 effects via their coupling to distinct signaling pathways...
  55. ncbi Prostanoid receptors of murine NIH 3T3 and RAW 264.7 cells. Structure and expression of the murine prostaglandin EP4 receptor gene
    T Arakawa
    Department of Biochemistry, Michigan State University, East Lansing, Michigan 48824, USA
    J Biol Chem 271:29569-75. 1996
    ..The levels of the EP2 and EP4 prostaglandin E2 (PGE2) receptors and the prostaglandin I2 receptor were changed in these cells by serum or LPS ..
  56. ncbi Colon carcinoma cell growth is associated with prostaglandin E2/EP4 receptor-evoked ERK activation
    Ambra Pozzi
    Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    J Biol Chem 279:29797-804. 2004
    ..The anti-proliferative effects of COX inhibition are rescued specifically by treatment with PGE(2) or the EP4 receptor-selective agonist PGE(1)-OH via phosphatidylinositol 3-kinase/extracellular signal-regulated kinase (ERK) ..
  57. ncbi Cloning and expression of a cDNA for mouse prostaglandin E receptor EP2 subtype
    A Honda
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan
    J Biol Chem 268:7759-62. 1993
    ..These results suggest that this receptor is EP2 subtype. Northern blot analysis demonstrated that the EP2 mRNA is widely expressed in various tissues, the abundant expression being observed in ileum, thymus, and mastocytoma P-815 cells...
  58. ncbi Role of EP4 prostaglandin E2 receptor in the ischemic liver
    Y Kuzumoto
    Department of Surgery, Nara Medical University School of Medicine, Nara, Japan
    Transplant Proc 37:422-4. 2005
    ..Recent studies have suggested the physiological and pathological role of EP4 in various inflammatory diseases...
  59. ncbi Osteopenia and impaired fracture healing in aged EP4 receptor knockout mice
    M Li
    Osteoporosis Research, Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, MS8118W 208, Groton, CT 06340, USA
    Bone 37:46-54. 2005
    The EP4 receptor, one of the subtypes of the prostaglandin E2 (PGE2) receptor, plays a critical role in the anabolic effects of PGE2 on bone...
  60. ncbi Biphasic effect of prostaglandin E2 on osteoclast formation in spleen cell cultures: role of the EP2 receptor
    Katsuhiro Ono
    Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030, USA
    J Bone Miner Res 20:23-9. 2005
    ..A selective EP2 receptor agonist mimicked these effects. Deletion of the EP2 receptor or depletion of T-cells abrogated the increase in OC number...
  61. ncbi Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I2 receptor IP
    Takayuki Fujino
    Department of Pharmacology, Asahikawa Medical College, Japan
    J Clin Invest 114:805-12. 2004
    ..These results indicate that PGI2 derived from COX-2 plays a critical role in regulating the release of renin and consequently renovascular hypertension in vivo...
  62. ncbi Thromboxane A2 and prostaglandin F2alpha mediate inflammatory tachycardia
    Koji Takayama
    Department of Pharmacology, Asahikawa Medical College, Midorigaoka Higashi 2 1 1 1, Asahikawa 078 8510, Japan
    Nat Med 11:562-6. 2005
    ..Our results show that inflammatory tachycardia is caused by a direct action on the heart of TXA(2) and PGF(2alpha) formed under systemic inflammatory conditions...
  63. ncbi Microarray evaluation of EP4 receptor-mediated prostaglandin E2 suppression of 3T3-L1 adipocyte differentiation
    Yukihiko Sugimoto
    Department of Physiological Chemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Sakyo ku, Kyoto 606 8501, Japan
    Biochem Biophys Res Commun 322:911-7. 2004
    ..extent PGE(2) inhibits the differentiation of cells to adipocytes and to examine whether its effect could be due to EP4 receptor signaling, we used microarrays to analyze the gene expression profiles of 3T3-L1 cells exposed to a ..
  64. ncbi PGE2-receptor subtype EP4-dependent adherence of mastocytoma P-815 cells to matrix components in subcutaneous tissues overlaying inside surface of air pouch cavity in CDF1 mouse
    H Kataoka
    School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women s University, 11 68 Kyuban cho, Koshien, Nishinomiya, Hyogo, 663 8179, Japan
    Inflamm Res 57:362-6. 2008
    ..We previously reported that PGE2-receptor EP4 stimulated the adhesion of mouse mastocytoma P-815 cells to plate-bound fibronectin...
  65. ncbi Protective effect of prostaglandin E2 receptors EP2 and EP4 in alloimmune response in vivo
    T Nomi
    Department of Surgery, Nara Medical University, Nara, Japan
    Transplant Proc 38:3209-10. 2006
    ..responses mediating a variety of both innate and adaptive immune responses through 4 distinct receptors: EP1 to EP4. The use of gene-targeted mice and selective agonists/antagonists responsible for each receptor has gradually ..
  66. ncbi Angiotensin II and III suppress food intake via angiotensin AT(2) receptor and prostaglandin EP(4) receptor in mice
    Kousaku Ohinata
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan
    FEBS Lett 582:773-7. 2008
    ..Taken together, centrally administered Ang II and III may decrease food intake through AT(2) receptor with partial involvement of AT(1) receptor, followed by EP(4) receptor activation, which is a novel pathway regulating food intake...
  67. ncbi Host and direct antitumor effects and profound reduction in tumor metastasis with selective EP4 receptor antagonism
    Li Yang
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Cancer Res 66:9665-72. 2006
    ..Here, we show that one of the PGE(2) receptors, the EP4 receptor, plays an important role in metastasis in both of these tumor types. Using i.v...
  68. ncbi A nonprostanoid EP4 receptor selective prostaglandin E2 agonist restores bone mass and strength in aged, ovariectomized rats
    Hua Zhu Ke
    Pfizer Global Research and Development, Groton Laboratories, Groton, Connecticut, USA
    J Bone Miner Res 21:565-75. 2006
    CP432 is a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E2 agonist...
  69. ncbi MyD88 plays a unique role in host defense but not arthritis development in Lyme disease
    Devin D Bolz
    Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
    J Immunol 173:2003-10. 2004
    ..The findings presented here point to a dichotomy between the recruitment of inflammatory cells to tissue and an inability of these cells to kill localized spirochetes...
  70. ncbi Mapping of six germ-cell-specific genes to mouse chromosomes
    M Matsui
    Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan
    Mamm Genome 8:873-4. 1997
  71. ncbi Cellular localization of mRNAs for prostaglandin E receptor subtypes in mouse gastrointestinal tract
    K Morimoto
    Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan
    Am J Physiol 272:G681-7. 1997
    ..Expression of EP4 mRNA was moderate in surface epithelial cells of the corpus and in glands from the surface to the base of the ..
  72. ncbi Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+ CD25+ T regulatory cell activities in lung cancer
    Sherven Sharma
    Department of Medicine, Lung Cancer Research Program, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095 1960, USA
    Cancer Res 65:5211-20. 2005
    ..that PGE2-mediated induction of Treg cell Foxp3 gene expression was significantly reduced in the absence of the EP4 receptor and ablated in the absence of the EP2 receptor expression...
  73. ncbi Prostaglandin E2 receptors EP2 and EP4 are down-regulated during differentiation of mouse osteoclasts from their precursors
    Yasuhiro Kobayashi
    Institute for Oral Science, Matsumoto Dental University, 1780 Hiro oka Gobara, Shiojiri, Nagano 399 0781, Japan
    J Biol Chem 280:24035-42. 2005
    ..Bone marrow macrophage osteoclast precursors expressed PGE2 receptors EP1, EP2, EP3beta, and EP4, and the expression of EP2 and EP4 was down-regulated during osteoclastic differentiation induced by receptor ..
  74. ncbi Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice
    M Sonoshita
    Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan
    Nat Med 7:1048-51. 2001
    ....
  75. ncbi Receptors for prostaglandin E(2) that regulate cellular immune responses in the mouse
    C Nataraj
    Division of Nephrology, Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705, USA
    J Clin Invest 108:1229-35. 2001
    ..There are four receptors for PGE(2) (EP1-EP4) with unique patterns of expression and different coupling to intracellular signaling pathways...
  76. ncbi Recruitment of a prostaglandin E receptor subtype, EP3-expressing bone marrow cells is crucial in wound-induced angiogenesis
    Emi Kamoshita
    Department of Pharmacology, Kitasato University School of Medicine, Kanagawa 228 8555, Japan
    Am J Pathol 169:1458-72. 2006
    ..EP3-/-) were significantly delayed compared with their wild-type (WT) mice, whereas those in EP1-/-, EP2-/-, and EP4-/- were not delayed...
  77. ncbi The effect of deletion of cyclooxygenase-2, prostaglandin receptor EP2, or EP4 in bone marrow cells on osteoclasts induced by mouse mammary cancer cell lines
    Katsuhiro Ono
    Department of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
    Bone 33:798-804. 2003
    ..There are four PGE(2) receptors but only the EP2 and EP4 receptors are reported to be important for OC formation...
  78. ncbi Cyclooxygenase-2/prostaglandin E2 accelerates the healing of gastric ulcers via EP4 receptors
    Ryo Hatazawa
    Dept of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical Univ, Misasagi, Yamashina, Kyoto 607, Japan
    Am J Physiol Gastrointest Liver Physiol 293:G788-97. 2007
    ..healing in mice caused by indomethacin was significantly reversed by the coadministration of 11-deoxy-PGE1 (EP3/EP4 agonist) but not other prostanoids, including the EP1, EP2, and EP3 agonists...

Research Grants14

  1. Control of Tumor Growth by the MMP/Angiostatin Pathway
    Ambra Pozzi; Fiscal Year: 2006
    ..These studies will help us to determine how stinaulation of the MMP/angiostatin axis can be used as a tool to inhibit specifically tumor vaseularization and growth. ..
  2. Control of Tumor Growth by the MMP/Angiostatin Pathway
    Ambra Pozzi; Fiscal Year: 2003
    ..These studies will help us to determine how stinaulation of the MMP/angiostatin axis can be used as a tool to inhibit specifically tumor vaseularization and growth. ..
  3. Control of Tumor Growth by the MMP/Angiostatin Pathway
    Ambra Pozzi; Fiscal Year: 2007
    ..These studies will help us to determine how stinaulation of the MMP/angiostatin axis can be used as a tool to inhibit specifically tumor vaseularization and growth. ..
  4. Role of Cyclooxygenase stimulated Neovascularization in Diabetic Nephropathy
    Ambra Pozzi; Fiscal Year: 2007
    ..diabetic kidneys, ii) PGE2 stimulates angiogenesis, iii) PGE2 increases endothelial permeability, and iv) the PGE2 EP4 receptor is highly expressed in glomeruli, we hypothesize that a functional prostaglandin dependent pathway is ..