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

Top Publications

  1. Kuzumoto Y, Sho M, Ikeda N, Hamada K, Mizuno T, Akashi S, et al. Significance and therapeutic potential of prostaglandin E2 receptor in hepatic ischemia/reperfusion injury in mice. Hepatology. 2005;42:608-17 pubmed
    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...
  2. Kundu N, Ma X, Holt D, Goloubeva O, Ostrand Rosenberg S, Fulton A. Antagonism of the prostaglandin E receptor EP4 inhibits metastasis and enhances NK function. Breast Cancer Res Treat. 2009;117:235-42 pubmed publisher
    ..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 ..
  3. Zhan P, Alander C, Kaneko H, Pilbeam C, Guan Y, Zhang Y, et al. Effect of deletion of the prostaglandin EP4 receptor on stimulation of calcium release from cultured mouse calvariae: impaired responsiveness in heterozygotes. Prostaglandins Other Lipid Mediat. 2005;78:19-26 pubmed
    The ability of prostaglandin E2 (PGE2), selective receptor agonists for EP2 and EP4 receptors (EP2A and EP4A) and parathyroid hormone (PTH) to stimulate calcium release from cultured fetal mouse calvariae was compared in wild type (WT) ..
  4. Rao R, Redha R, Macias Perez I, Su Y, Hao C, Zent R, et al. Prostaglandin E2-EP4 receptor promotes endothelial cell migration via ERK activation and angiogenesis in vivo. J Biol Chem. 2007;282:16959-68 pubmed
    ..The present study examined the role of the EP4 receptor in regulating endothelial cell proliferation, migration, and tubulogenesis...
  5. Kobayashi Y, Take I, Yamashita T, Mizoguchi T, Ninomiya T, Hattori T, et al. Prostaglandin E2 receptors EP2 and EP4 are down-regulated during differentiation of mouse osteoclasts from their precursors. J Biol Chem. 2005;280:24035-42 pubmed
    ..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 ..
  6. Kunikata T, Yamane H, Segi E, Matsuoka T, Sugimoto Y, Tanaka S, et al. Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3. Nat Immunol. 2005;6:524-31 pubmed
    ..Thus, the PGE(2)-EP3 pathway is an important negative modulator of allergic reactions. ..
  7. Boniface K, Bak Jensen K, Li Y, Blumenschein W, McGeachy M, McClanahan T, et al. Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling. J Exp Med. 2009;206:535-48 pubmed publisher
    ..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...
  8. Nguyen M, Camenisch T, Snouwaert J, Hicks E, Coffman T, Anderson P, et al. The prostaglandin receptor EP4 triggers remodelling of the cardiovascular system at birth. Nature. 1997;390:78-81 pubmed
    ..This requirement is absent in mice lacking the prostaglandin E2 EP4 receptor (EP4(-/-) mice)...
  9. Segi E, Sugimoto Y, Yamasaki A, Aze Y, Oida H, Nishimura T, et al. Patent ductus arteriosus and neonatal death in prostaglandin receptor EP4-deficient mice. Biochem Biophys Res Commun. 1998;246:7-12 pubmed
    The physiological role of the prostaglandin E2 receptor EP4 subtype was investigated by generation of EP4-deficient-mice by gene targeting...

More Information


  1. Schneider A, Guan Y, Zhang Y, Magnuson M, Pettepher C, Loftin C, et al. Generation of a conditional allele of the mouse prostaglandin EP4 receptor. Genesis. 2004;40:7-14 pubmed
    Genetic disruption of the mouse EP4 receptor results in perinatal lethality associated with persistent patent ductus areteriosus (PDA)...
  2. Kamoshita E, Ikeda Y, Fujita M, Amano H, Oikawa A, Suzuki T, et al. Recruitment of a prostaglandin E receptor subtype, EP3-expressing bone marrow cells is crucial in wound-induced angiogenesis. Am J Pathol. 2006;169:1458-72 pubmed
    ..EP3-/-) were significantly delayed compared with their wild-type (WT) mice, whereas those in EP1-/-, EP2-/-, and EP4-/- were not delayed...
  3. Yang L, Huang Y, Porta R, Yanagisawa K, Gonzalez A, Segi E, et al. Host and direct antitumor effects and profound reduction in tumor metastasis with selective EP4 receptor antagonism. Cancer Res. 2006;66:9665-72 pubmed
    ..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...
  4. Kabashima K, Sakata D, Nagamachi M, Miyachi Y, Inaba K, Narumiya S. Prostaglandin E2-EP4 signaling initiates skin immune responses by promoting migration and maturation of Langerhans cells. Nat Med. 2003;9:744-9 pubmed
    ..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...
  5. Matsuoka Y, Furuyashiki T, Bito H, Ushikubi F, Tanaka Y, Kobayashi T, et al. Impaired adrenocorticotropic hormone response to bacterial endotoxin in mice deficient in prostaglandin E receptor EP1 and EP3 subtypes. Proc Natl Acad Sci U S A. 2003;100:4132-7 pubmed
    ..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 ..
  6. Kabashima K, Saji T, Murata T, Nagamachi M, Matsuoka T, Segi E, et al. The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut. J Clin Invest. 2002;109:883-93 pubmed
    ..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% ..
  7. Holt D, Ma X, Kundu N, Collin P, Fulton A. Modulation of host natural killer cell functions in breast cancer via prostaglandin E2 receptors EP2 and EP4. J Immunother. 2012;35:179-88 pubmed publisher
    ..published data indicate that inhibiting either PGE2 production or PGE2-mediated signaling through the PGE2 receptor EP4 (1 of 4 EP expressed on the malignant cell) reduces metastasis by a mechanism that requires natural killer (NK) ..
  8. Sharma S, Yang S, Zhu L, Reckamp K, Gardner B, Baratelli F, et al. Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+ CD25+ T regulatory cell activities in lung cancer. Cancer Res. 2005;65:5211-20 pubmed
    ..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...
  9. McCoy J, Wicks J, Audoly L. The role of prostaglandin E2 receptors in the pathogenesis of rheumatoid arthritis. J Clin Invest. 2002;110:651-8 pubmed
    ..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...
  10. Mutoh M, Watanabe K, Kitamura T, Shoji Y, Takahashi M, Kawamori T, et al. Involvement of prostaglandin E receptor subtype EP(4) in colon carcinogenesis. Cancer Res. 2002;62:28-32 pubmed
  11. Zahner G, Schaper M, Panzer U, Kluger M, Stahl R, Thaiss F, et al. Prostaglandin EP2 and EP4 receptors modulate expression of the chemokine CCL2 (MCP-1) in response to LPS-induced renal glomerular inflammation. Biochem J. 2009;422:563-70 pubmed publisher more pronounced in MCs lacking the PGE2 (prostaglandin E2) receptor EP2 or in MCs treated with a prostaglandin EP4 receptor antagonist...
  12. Xie C, Liang B, Xue M, Lin A, Loiselle A, Schwarz E, et al. Rescue of impaired fracture healing in COX-2-/- mice via activation of prostaglandin E2 receptor subtype 4. Am J Pathol. 2009;175:772-85 pubmed publisher
    ..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 ..
  13. Tang E, Shimizu K, Christen T, Rocha V, Shvartz E, Tesmenitsky Y, et al. Lack of EP4 receptors on bone marrow-derived cells enhances inflammation in atherosclerotic lesions. Cardiovasc Res. 2011;89:234-43 pubmed publisher
    prostaglandin E(2), by ligation of its receptor EP4, suppresses the production of inflammatory cytokines and chemokines in macrophages in vitro. Thus, activation of EP4 may constitute an endogenous anti-inflammatory pathway...
  14. Stitt Cavanagh E, Faour W, Takami K, Carter A, Vanderhyden B, Guan Y, et al. A maladaptive role for EP4 receptors in podocytes. J Am Soc Nephrol. 2010;21:1678-90 pubmed publisher
    ..e., mechanical stretch) along with prostaglandin E(2) stimulation of its EP4 receptor induced cyclooxygenase-2 in a p38-dependent manner...
  15. Subbaramaiah K, Hudis C, Chang S, Hla T, Dannenberg A. EP2 and EP4 receptors regulate aromatase expression in human adipocytes and breast cancer cells. Evidence of a BRCA1 and p300 exchange. J Biol Chem. 2008;283:3433-44 pubmed
    ..Reciprocal changes in the interaction between BRCA1, p300, and the aromatase promoter I.3/II contributed to the inductive effects of PGE(2). ..
  16. Minami M, Shimizu K, Okamoto Y, Folco E, Ilasaca M, Feinberg M, et al. Prostaglandin E receptor type 4-associated protein interacts directly with NF-kappaB1 and attenuates macrophage activation. J Biol Chem. 2008;283:9692-703 pubmed publisher
    ..Through the receptor EP4, prostaglandin E(2) (PGE(2)) exerts an anti-inflammatory action in macrophages, suppressing stimulus-induced ..
  17. Shi J, Johansson J, Woodling N, Wang Q, Montine T, Andreasson K. The prostaglandin E2 E-prostanoid 4 receptor exerts anti-inflammatory effects in brain innate immunity. J Immunol. 2010;184:7207-18 pubmed publisher
    ..We report that PGE2 EP4 signaling mediates an anti-inflammatory effect in brain by blocking LPS-induced proinflammatory gene expression in ..
  18. Faour W, Gomi K, Kennedy C. PGE(2) induces COX-2 expression in podocytes via the EP(4) receptor through a PKA-independent mechanism. Cell Signal. 2008;20:2156-64 pubmed publisher
    ..This PGE(2)-induced signaling network activated by increased P(gc) could be detrimental to podocyte health and glomerular filtration barrier integrity. ..
  19. Nguyen M, Pace A, Koller B. Age-induced reprogramming of mast cell degranulation. J Immunol. 2005;175:5701-7 pubmed
    ..Therefore, elevated PGE2 levels might provide an important pathway by which mast cells are engaged to participate in inflammatory responses in the elderly patient. ..
  20. Hori R, Nakagawa T, Sugimoto Y, Sakamoto T, Yamamoto N, Hamaguchi K, et al. Prostaglandin E receptor subtype EP4 agonist protects cochleae against noise-induced trauma. Neuroscience. 2009;160:813-9 pubmed publisher 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...
  21. Nusing R, Treude A, Weissenberger C, Jensen B, Bek M, Wagner C, et al. Dominant role of prostaglandin E2 EP4 receptor in furosemide-induced salt-losing tubulopathy: a model for hyperprostaglandin E syndrome/antenatal Bartter syndrome. J Am Soc Nephrol. 2005;16:2354-62 pubmed
    ..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 ..
  22. Gao Q, Zhan P, Alander C, Kream B, Hao C, Breyer M, et al. 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. Bone. 2009;45:98-103 pubmed publisher
    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...
  23. Yao C, Sakata D, Esaki Y, Li Y, Matsuoka T, Kuroiwa K, et al. Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion. Nat Med. 2009;15:633-40 pubmed publisher
    ..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-..
  24. Narumiya S, Sugimoto Y, Ushikubi F. Prostanoid receptors: structures, properties, and functions. Physiol Rev. 1999;79:1193-226 pubmed
    ..In this article, we summarize these findings and attempt to give an overview of the current status of research on the prostanoid receptors...
  25. Ushikubi F, Segi E, Sugimoto Y, Murata T, Matsuoka T, Kobayashi T, et al. Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3. Nature. 1998;395:281-4 pubmed
    ..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...
  26. Harding P, Yang X, Yang J, Shesely E, He Q, LaPointe M. Gene expression profiling of dilated cardiomyopathy in older male EP4 knockout mice. Am J Physiol Heart Circ Physiol. 2010;298:H623-32 pubmed publisher
    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...
  27. Huang S, White E, Wettlaufer S, Grifka H, Hogaboam C, Thannickal V, et al. Prostaglandin E(2) induces fibroblast apoptosis by modulating multiple survival pathways. FASEB J. 2009;23:4317-26 pubmed publisher
    ..These proapoptotic actions were dependent on signaling through the EP2/EP4 receptors and by downstream activation of both caspases 8 and 9...
  28. Tang E, Shvartz E, Shimizu K, Rocha V, Zheng C, Fukuda D, et al. Deletion of EP4 on bone marrow-derived cells enhances inflammation and angiotensin II-induced abdominal aortic aneurysm formation. Arterioscler Thromb Vasc Biol. 2011;31:261-9 pubmed publisher
    To examine whether a lack of prostaglandin E receptor 4 (EP4) on bone marrow-derived cells would increase local inflammation and enhance the formation of abdominal aortic aneurysm (AAA) in vivo...
  29. Ikushima Y, Arai F, Hosokawa K, Toyama H, Takubo K, Furuyashiki T, et al. Prostaglandin E(2) regulates murine hematopoietic stem/progenitor cells directly via EP4 receptor and indirectly through mesenchymal progenitor cells. Blood. 2013;121:1995-2007 pubmed publisher
    ..However, the receptor(s) responsible for PGE(2) signaling remains unclear. Here, we identified EP4 as a receptor activated by PGE(2) to regulate HSPCs...
  30. Park T, Baik E, Lee S. Prostaglandin E?-induced intercellular adhesion molecule-1 expression is mediated by cAMP/Epac signalling modules in bEnd.3 brain endothelial cells. Br J Pharmacol. 2013;169:604-18 pubmed publisher
    ..PGE? significantly up-regulated the expression of ICAM-1, which was blocked by EP4 antagonist (ONO-AE2-227) and knock-down of EP4...
  31. Idell S, James K, Levin E, Schwartz B, Manchanda N, Maunder R, et al. Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult respiratory distress syndrome. J Clin Invest. 1989;84:695-705 pubmed
    ..We conclude that abnormalities that result in enhanced coagulation and depressed fibrinolysis, thereby predisposing to alveolar fibrin deposition, occur in the alveolar lining fluids from patients with ARDS. ..
  32. Wang H, Xie H, Sun X, Tranguch S, Zhang H, Jia X, et al. Stage-specific integration of maternal and embryonic peroxisome proliferator-activated receptor delta signaling is critical to pregnancy success. J Biol Chem. 2007;282:37770-82 pubmed
    ..This study is clinically relevant because deferral of on time implantation leads to spontaneous pregnancy loss, and defective trophoblast invasion is one cause of preeclampsia in humans. ..
  33. Zhang M, Yao B, Wang Y, Yang S, Wang S, Fan X, et al. Inhibition of cyclooxygenase-2 in hematopoietic cells results in salt-sensitive hypertension. J Clin Invest. 2015;125:4281-94 pubmed publisher
    ..either COX-2-deficient or mPGES-1-deficient mice into WT mice or macrophage-specific deletion of the PGE2 type 4 (EP4) receptor induced salt-sensitive hypertension and increased phosphorylation of the renal sodium chloride ..
  34. Hatazawa R, Tanaka A, Tanigami M, Amagase K, Kato S, Ashida Y, et al. Cyclooxygenase-2/prostaglandin E2 accelerates the healing of gastric ulcers via EP4 receptors. Am J Physiol Gastrointest Liver Physiol. 2007;293:G788-97 pubmed
    ..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...
  35. Hamaguchi K, Yamamoto N, Nakagawa T, Furuyashiki T, Narumiya S, Ito J. Role of PGE-type receptor 4 in auditory function and noise-induced hearing loss in mice. Neuropharmacology. 2012;62:1841-7 pubmed publisher
    This study explored the physiological roles of PGE-type receptor 4 (EP4) in auditory function...
  36. Akhter M, Cullen D, Pan L. Bone biomechanical properties in EP4 knockout mice. Calcif Tissue Int. 2006;78:357-62 pubmed
    ..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. ..
  37. Fabre J, Nguyen M, Athirakul K, Coggins K, McNeish J, Austin S, et al. Activation of the murine EP3 receptor for PGE2 inhibits cAMP production and promotes platelet aggregation. J Clin Invest. 2001;107:603-10 pubmed
    ..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...
  38. Wang X, Yao B, Wang Y, Fan X, Wang S, Niu A, et al. Macrophage Cyclooxygenase-2 Protects Against Development of Diabetic Nephropathy. Diabetes. 2017;66:494-504 pubmed publisher
  39. Cao R, St Amand T, Li X, Yoon S, Wang C, Song H, et al. Prostaglandin receptor EP4 in abdominal aortic aneurysms. Am J Pathol. 2012;181:313-21 pubmed publisher
    ..In this study, we used this model to examine the role of the prostaglandin E receptor subtype 4 (EP4) and genetic knockdown of COX-2 expression (70% to 90%) in AAA pathogenesis...
  40. Tomita M, Li X, Okada Y, Woodiel F, Young R, Pilbeam C, et al. Effects of selective prostaglandin EP4 receptor antagonist on osteoclast formation and bone resorption in vitro. Bone. 2002;30:159-63 pubmed
    ..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...
  41. Ma X, Aoki T, Narumiya S. Prostaglandin E2-EP4 signaling persistently amplifies CD40-mediated induction of IL-23 p19 expression through canonical and non-canonical NF-κB pathways. Cell Mol Immunol. 2016;13:240-50 pubmed publisher
    ..prostaglandin (PG) E2 promotes CD40-mediated induction of Il23a (p19) expression through its E receptor subtype 4 (EP4) receptor in splenic dendritic cells (DCs)...
  42. Hori R, Nakagawa T, Yamamoto N, Hamaguchi K, Ito J. Role of prostaglandin E receptor subtypes EP2 and EP4 in autocrine and paracrine functions of vascular endothelial growth factor in the inner ear. BMC Neurosci. 2010;11:35 pubmed publisher
    ..E1 (PGE1) and prostaglandin E2 (PGE2) are mediated by the prostaglandin E receptor subtypes EP1, EP2, EP3, and EP4, and the respective agonists have been purified...
  43. Wu X, Zeng L, Taniguchi T, Xie Q. Activation of PKA and phosphorylation of sodium-dependent vitamin C transporter 2 by prostaglandin E2 promote osteoblast-like differentiation in MC3T3-E1 cells. Cell Death Differ. 2007;14:1792-801 pubmed
    ..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...
  44. Németh K, Leelahavanichkul A, Yuen P, Mayer B, Parmelee A, Doi K, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2009;15:42-9 pubmed publisher
    ..macrophages by releasing prostaglandin E(2) that acts on the macrophages through the prostaglandin EP2 and EP4 receptors...
  45. Akaogi J, Yamada H, Kuroda Y, Nacionales D, Reeves W, Satoh M. 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. J Leukoc Biol. 2004;76:227-36 pubmed
    ..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 ..
  46. Sonoshita M, Takaku K, Sasaki N, Sugimoto Y, Ushikubi F, Narumiya S, et al. Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice. Nat Med. 2001;7:1048-51 pubmed
  47. Ho A, Palla A, Blake M, Yucel N, Wang Y, Magnusson K, et al. Prostaglandin E2 is essential for efficacious skeletal muscle stem-cell function, augmenting regeneration and strength. Proc Natl Acad Sci U S A. 2017;114:6675-6684 pubmed publisher
    ..Here we show that Prostaglandin E2 (PGE2) is an inflammatory cytokine that directly targets MuSCs via the EP4 receptor, leading to MuSC expansion...
  48. Thibodeau J, Holterman C, He Y, Carter A, Cron G, Boisvert N, et al. Vascular Smooth Muscle-Specific EP4 Receptor Deletion in Mice Exacerbates Angiotensin II-Induced Renal Injury. Antioxid Redox Signal. 2016;25:642-656 pubmed
    ..We hypothesized that vascular smooth muscle prostaglandin E2 (PGE2) E-prostanoid 4 (EP4) receptor deletion predisposes to renal injury via unchecked vasoconstrictive actions of angiotensin II (AngII) in ..
  49. Ohinata K, Suetsugu K, Fujiwara Y, Yoshikawa M. Activation of prostaglandin E receptor EP4 subtype suppresses food intake in mice. Prostaglandins Other Lipid Mediat. 2006;81:31-6 pubmed
    ..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...
  50. Jones V, Birrell M, Maher S, Griffiths M, Grace M, O Donnell V, et al. Role of EP2 and EP4 receptors in airway microvascular leak induced by prostaglandin E2. Br J Pharmacol. 2016;173:992-1004 pubmed publisher
    ..A significant reduction in PGE2-induced MVL was demonstrated in Ptger2−/− and Ptger4−/− mice and in wild-type mice pretreated simultaneously with EP2 (PF-04418948) and EP4 (ER-819762) ..
  51. Gao M, Cao R, Du S, Jia X, Zheng S, Huang S, et al. Disruption of prostaglandin E2 receptor EP4 impairs urinary concentration via decreasing aquaporin 2 in renal collecting ducts. Proc Natl Acad Sci U S A. 2015;112:8397-402 pubmed publisher
    ..Recently, prostaglandin E2 (PGE2) receptor EP4 has emerged as a potential therapeutic target for the treatment of nephrogenic diabetes insipidus, but the ..
  52. Kundu N, Ma X, Kochel T, Goloubeva O, Staats P, Thompson K, et al. Prostaglandin E receptor EP4 is a therapeutic target in breast cancer cells with stem-like properties. Breast Cancer Res Treat. 2014;143:19-31 pubmed publisher
    ..Prostaglandin E receptor 4 (EP4) is widely expressed in primary invasive ductal carcinomas of the breast and antagonizing this receptor with small ..
  53. Mohamed R, Jayakumar C, Ramesh G. Chronic administration of EP4-selective agonist exacerbates albuminuria and fibrosis of the kidney in streptozotocin-induced diabetic mice through IL-6. Lab Invest. 2013;93:933-45 pubmed publisher
    ..Here, we show the cross talk of the PGE2-EP4 pathways and IL-6 in inducing albuminuria and fibrosis in an animal model of type 1 diabetes...
  54. Yang Z, Das S, Wang J, Sugimoto Y, Ichikawa A, Dey S. Potential sites of prostaglandin actions in the periimplantation mouse uterus: differential expression and regulation of prostaglandin receptor genes. Biol Reprod. 1997;56:368-79 pubmed
    ..PGE2 receptors are classified into four subtypes, EP1, EP2, EP3, and EP4. While EP1 is coupled to Ca2+ mobilization, activation of EP2 and EP4 triggers stimulation of adenylyl cyclase...
  55. Oskolkova O, Gawlak G, Tian Y, Ke Y, Sarich N, Son S, et al. Prostaglandin E receptor-4 receptor mediates endothelial barrier-enhancing and anti-inflammatory effects of oxidized phospholipids. FASEB J. 2017;31:4187-4202 pubmed publisher
    ..Results show that only prostaglandin E receptor-4 (EP4) was involved and mediated the sustained phase of the barrier-enhancing effects of OxPAPC that are associated with ..
  56. Hoshino T, Namba T, Takehara M, Murao N, Matsushima T, Sugimoto Y, et al. Improvement of cognitive function in Alzheimer's disease model mice by genetic and pharmacological inhibition of the EP(4) receptor. J Neurochem. 2012;120:795-805 pubmed publisher
    ..We therefore propose that EP(4) receptor antagonists, such as AE3-208, could be therapeutically beneficial for the prevention and treatment of AD. ..
  57. Hosono K, Isonaka R, Kawakami T, Narumiya S, Majima M. Signaling of Prostaglandin E Receptors, EP3 and EP4 Facilitates Wound Healing and Lymphangiogenesis with Enhanced Recruitment of M2 Macrophages in Mice. PLoS ONE. 2016;11:e0162532 pubmed publisher
    ..Mice lacking either EP3 or EP4 exhibited reduced wound-healing, lymphangiogenesis and recruitment of M2 macrophages, compared with wild type mice...
  58. Yokoyama U, Minamisawa S, Quan H, Ghatak S, Akaike T, Segi Nishida E, et al. Chronic activation of the prostaglandin receptor EP4 promotes hyaluronan-mediated neointimal formation in the ductus arteriosus. J Clin Invest. 2006;116:3026-34 pubmed
    ..Genetic disruption of the PGE-specific receptor EP4, however, paradoxically results in fatal patent DA (PDA) in mice...
  59. Mitani K, Sekiguchi F, Maeda T, Tanaka Y, Yoshida S, Kawabata A. The prostaglandin E2/EP4 receptor/cyclic AMP/T-type Ca(2+) channel pathway mediates neuritogenesis in sensory neuron-like ND7/23 cells. J Pharmacol Sci. 2016;130:177-80 pubmed publisher
    ..PGE2 caused neuritogenesis, an effect abolished by an EP4 receptor antagonist or inhibitors of adenylyl cyclase (AC) or protein kinase A (PKA) and mimicked by the AC ..
  60. Miyoshi H, VanDussen K, Malvin N, Ryu S, Wang Y, Sonnek N, et al. Prostaglandin E2 promotes intestinal repair through an adaptive cellular response of the epithelium. EMBO J. 2017;36:5-24 pubmed publisher
    ..cell culture system, we found that prostaglandin E2 (PGE2) signaling through one of its receptors, Ptger4, was sufficient to drive a differentiation state morphologically and transcriptionally similar to in vivo WAE ..
  61. Li F, He B, Ma X, Yu S, Bhave R, Lentz S, et al. Prostaglandin E1 and Its Analog Misoprostol Inhibit Human CML Stem Cell Self-Renewal via EP4 Receptor Activation and Repression of AP-1. Cell Stem Cell. 2017;21:359-373.e5 pubmed publisher
    ..Mechanistically, PGE1 acted on the EP4 receptor and repressed Fosb and Fos AP-1 factors in a ?-catenin-independent manner...
  62. Omori K, Kida T, Hori M, Ozaki H, Murata T. Multiple roles of the PGE2 -EP receptor signal in vascular permeability. Br J Pharmacol. 2014;171:4879-89 pubmed publisher
    ..Local administration of PGE2 , an EP2 or EP4 receptor agonist into FVB/NJcl mouse ear skin caused vascular leakage, indicated by dye extravasation...
  63. Tunaru S, Althoff T, Nusing R, Diener M, Offermanns S. Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors. Proc Natl Acad Sci U S A. 2012;109:9179-84 pubmed publisher
    ..These findings identify the cellular and molecular mechanism underlying the pharmacological effects of castor oil and indicate a role of the EP(3) receptor as a target to induce laxative effects. ..
  64. Frölich S, Olliges A, Kern N, Schreiber Y, Narumiya S, Nusing R. Temporal expression of the PGE2 synthetic system in the kidney is associated with the time frame of renal developmental vulnerability to cyclooxygenase-2 inhibition. Am J Physiol Renal Physiol. 2012;303:F209-19 pubmed publisher
    ..glomerulogenesis in EP receptor knockout mice revealed a reduction in glomerular size in EP1(-/-), EP2(-/-), and EP4(-/-) mice, supporting the developmental role of PGE(2)...
  65. Vennemann A, Gerstner A, Kern N, Ferreiros Bouzas N, Narumiya S, Maruyama T, et al. PTGS-2-PTGER2/4 signaling pathway partially protects from diabetogenic toxicity of streptozotocin in mice. Diabetes. 2012;61:1879-87 pubmed publisher
    ..Diabetogenicity of STZ in PTGER1(-/-), PTGER2(-/-), PTGER3(-/-), and PTGER4(-/-) mice was comparable to control mice...
  66. Zhu Z, Fu C, Li X, Song Y, Li C, Zou M, et al. Prostaglandin E2 promotes endothelial differentiation from bone marrow-derived cells through AMPK activation. PLoS ONE. 2011;6:e23554 pubmed publisher
    ..and endothelial nitric oxide synthase, the target of activated AMPK, were both increased which could be blocked by EP4 blocking peptide and simulated by the agonist of EP4 but not EP1, EP2 or EP3...
  67. Nasrallah R, Xiong H, Hébert R. Renal prostaglandin E2 receptor (EP) expression profile is altered in streptozotocin and B6-Ins2Akita type I diabetic mice. Am J Physiol Renal Physiol. 2007;292:F278-84 pubmed
    ..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. ..
  68. Arakawa T, Laneuville O, Miller C, Lakkides K, Wingerd B, DeWitt D, et al. Prostanoid receptors of murine NIH 3T3 and RAW 264.7 cells. Structure and expression of the murine prostaglandin EP4 receptor gene. J Biol Chem. 1996;271:29569-75 pubmed
    ..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 ..
  69. Fuller J, Brady Wood S, Elias M. Effects of retinal degeneration and brain size upon spatial reversal learning in mice. Percept Mot Skills. 1973;36:947-50 pubmed
  70. Yokoyama U, Minamisawa S, Shioda A, Ishiwata R, Jin M, Masuda M, et al. Prostaglandin E2 inhibits elastogenesis in the ductus arteriosus via EP4 signaling. Circulation. 2014;129:487-96 pubmed publisher
    ..Stimulation of the prostaglandin E? (PGE?) receptor EP4 significantly inhibited elastogenesis and decreased lysyl oxidase (LOX) protein, which catalyzes elastin cross-..
  71. Kabashima K, Nagamachi M, Honda T, Nishigori C, Miyachi Y, Tokura Y, et al. Prostaglandin E2 is required for ultraviolet B-induced skin inflammation via EP2 and EP4 receptors. Lab Invest. 2007;87:49-55 pubmed
    ..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...
  72. Austin S, Funk C. Insight into prostaglandin, leukotriene, and other eicosanoid functions using mice with targeted gene disruptions. Prostaglandins Other Lipid Mediat. 1999;58:231-52 pubmed
    ..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. ..