EP4

Summary

Gene Symbol: EP4
Description: prostaglandin E receptor 4
Alias: EP4, EP4R, prostaglandin E2 receptor EP4 subtype, PGE receptor, EP4 subtype, PGE2 receptor EP4 subtype, prostaglandin E receptor 4 (subtype EP4), prostanoid EP4 receptor
Species: human
Products:     EP4

Top Publications

  1. Fujino H, West K, Regan J. Phosphorylation of glycogen synthase kinase-3 and stimulation of T-cell factor signaling following activation of EP2 and EP4 prostanoid receptors by prostaglandin E2. J Biol Chem. 2002;277:2614-9 pubmed
    ..This is the first indication of a fundamental difference in the signaling potential of EP(2) and EP(4) prostanoid receptors. ..
  2. 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
  3. Fujino H, Xu W, Regan J. Prostaglandin E2 induced functional expression of early growth response factor-1 by EP4, but not EP2, prostanoid receptors via the phosphatidylinositol 3-kinase and extracellular signal-regulated kinases. J Biol Chem. 2003;278:12151-6 pubmed
    ..These findings point to important differences in the signaling potential of the EP(2) and EP(4) receptors, which could be significant with respect to the potential involvement of EP(4) receptors in inflammation and cancer. ..
  4. Hawcroft G, Ko C, Hull M. Prostaglandin E2-EP4 receptor signalling promotes tumorigenic behaviour of HT-29 human colorectal cancer cells. Oncogene. 2007;26:3006-19 pubmed
    ..Expression of the PGE2 receptor EP4 is upregulated during colorectal carcinogenesis...
  5. Gustafsson A, Hansson E, Kressner U, Nordgren S, Andersson M, Wang W, et al. EP1-4 subtype, COX and PPAR gamma receptor expression in colorectal cancer in prediction of disease-specific mortality. Int J Cancer. 2007;121:232-40 pubmed
    ..Our results imply that both prostaglandin production (COX-2) and signaling via EP(1-4) subtype receptors, particularly EP(2), predict disease-specific mortality in colorectal cancer. ..
  6. Libioulle C, Louis E, Hansoul S, Sandor C, Farnir F, Franchimont D, et al. Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4. PLoS Genet. 2007;3:e58 pubmed
    ..that disease-associated alleles correlate with quantitative expression levels of the prostaglandin receptor EP4, PTGER4, the gene that resides closest to the associated region...
  7. Asano T, Shoda J, Ueda T, Kawamoto T, Todoroki T, Shimonishi M, et al. Expressions of cyclooxygenase-2 and prostaglandin E-receptors in carcinoma of the gallbladder: crucial role of arachidonate metabolism in tumor growth and progression. Clin Cancer Res. 2002;8:1157-67 pubmed
    ..In epithelial-stromal interactions, the increased PGE(2) synthesis in the adjacent stroma and its biological effect via EP(4) on the carcinoma cells may contribute to tumor growth and progression of gallbladder carcinoma. ..
  8. De Jager P, Jia X, Wang J, de Bakker P, Ottoboni L, Aggarwal N, et al. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat Genet. 2009;41:776-82 pubmed publisher
  9. Robertson F, Simeone A, Lucci A, McMurray J, Ghosh S, Cristofanilli M. Differential regulation of the aggressive phenotype of inflammatory breast cancer cells by prostanoid receptors EP3 and EP4. Cancer. 2010;116:2806-14 pubmed publisher
    ..Agonists and antagonists of the prostanoid receptors EP3 and EP4 and of EP4 short-hairpin RNA (shRNA) knockdown approaches were used as tools to assess the role of prostanoid ..

More Information

Publications107 found, 100 shown here

  1. Prijatelj M, Celhar T, Mlinaric Rascan I. Prostaglandin EP4 receptor enhances BCR-induced apoptosis of immature B cells. Prostaglandins Other Lipid Mediat. 2011;95:19-26 pubmed publisher
    ..Gene and protein expression analyses showed that, of the four PGE2 receptors subtypes, only EP4 receptor is upregulated upon BCR cross-linking, leading to sensitization of WEHI 231 cells towards PGE2 mediated ..
  2. Evans D, Spencer C, Pointon J, Su Z, Harvey D, Kochan G, et al. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat Genet. 2011;43:761-7 pubmed publisher
    ..These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides. ..
  3. Wu J, Zhang Y, Frilot N, Kim J, Kim W, Daaka Y. Prostaglandin E2 regulates renal cell carcinoma invasion through the EP4 receptor-Rap GTPase signal transduction pathway. J Biol Chem. 2011;286:33954-62 pubmed publisher
    ..that prostaglandin E(2) promotes renal cancer cell invasion through a signal transduction pathway that encompasses EP4 and small GTPase Rap...
  4. Glas J, Seiderer J, Czamara D, Pasciuto G, Diegelmann J, Wetzke M, et al. PTGER4 expression-modulating polymorphisms in the 5p13.1 region predispose to Crohn's disease and affect NF-?B and XBP1 binding sites. PLoS ONE. 2012;7:e52873 pubmed publisher
    ..Further functional studies are necessary to confirm the results of our in silico analysis and to analyze if changes in PTGER4 expression modulate CD susceptibility. ..
  5. Camacho M, Dilmé J, Solà Villà D, Rodriguez C, Bellmunt S, Siguero L, et al. Microvascular COX-2/mPGES-1/EP-4 axis in human abdominal aortic aneurysm. J Lipid Res. 2013;54:3506-15 pubmed publisher
    ..We provide new data concerning mPGES-1 expression in human AAA. Our findings suggest the potential relevance of the COX-2/mPGES-1/EP-4 axis in the AAA-associated hypervascularization. ..
  6. Cosme R, Lublin D, Takafuji V, Lynch K, Roche J. Prostanoids in human colonic mucosa: effects of inflammation on PGE(2) receptor expression. Hum Immunol. 2000;61:684-96 pubmed
    ..A major perturbation in the number and distribution of PGE(2) receptors and enzymes for prostanoid synthesis occurs in chronic inflammation of the colon, with consequences for mucosal T lymphocyte function. ..
  7. Takayama K, Sukhova G, Chin M, Libby P. A novel prostaglandin E receptor 4-associated protein participates in antiinflammatory signaling. Circ Res. 2006;98:499-504 pubmed
    Prostaglandin E2 exerts an antiinflammatory action by ligation of the heptahelical receptor EP4 in human macrophages...
  8. Kim S, Kim Y, Park H, Jee Y, Kim S, Bahn J, et al. Association between polymorphisms in prostanoid receptor genes and aspirin-intolerant asthma. Pharmacogenet Genomics. 2007;17:295-304 pubmed
    ..015). These findings suggest that genetic polymorphisms in PTGER2, PTGER3, PTGER4, PTGIR, and TBXA2R play important roles in the pathogenesis of aspirin-intolerant asthma. ..
  9. Cherukuri D, Chen X, Goulet A, Young R, Han Y, Heimark R, et al. The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells. Exp Cell Res. 2007;313:2969-79 pubmed
    ..PGE(2) exerts its effects through four G-protein-coupled PGE receptor (EP) subtypes, named the EP1, EP2, EP3, and EP4. Increased phosphorylation of extracellular regulated kinases (ERK1/2) is required for PGE(2) to stimulate cell ..
  10. Robertson F, Simeone A, Mazumdar A, Shah A, McMurray J, Ghosh S, et al. Molecular and pharmacological blockade of the EP4 receptor selectively inhibits both proliferation and invasion of human inflammatory breast cancer cells. J Exp Ther Oncol. 2008;7:299-312 pubmed
    ..is to block binding of the PGE2 ligand to its prostanoid (EP) receptors, which are designated as EP1, EP2, EP3, and EP4 and are members of a subfamily of G protein coupled receptors (GPCRs)...
  11. 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...
  12. Matesanz F, González Pérez A, Lucas M, Sanna S, Gayán J, Urcelay E, et al. Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1. PLoS ONE. 2012;7:e36140 pubmed publisher
    ..Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS. ..
  13. Franke A, Hampe J, Rosenstiel P, Becker C, Wagner F, Häsler R, et al. Systematic association mapping identifies NELL1 as a novel IBD disease gene. PLoS ONE. 2007;2:e691 pubmed
    ..Several associations were replicated in at least one independent sample, point to an involvement of ITGB6 (upstream), GRM8 (downstream), OR5V1 (downstream), PPP3R2 (downstream), NM_152575 (upstream) and HNF4G (intron). ..
  14. Kim H, Kim M, Park Y, Park I, Kim T, Yang S, et al. Prostaglandin E2 Activates YAP and a Positive-Signaling Loop to Promote Colon Regeneration After Colitis but Also Carcinogenesis in Mice. Gastroenterology. 2017;152:616-630 pubmed publisher
    ..synthase 2 gene (PTGS2 or cyclooxygenase 2) and prostaglandin E-receptor 4 gene (PTGER4 or EP4)...
  15. 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...
  16. Wang J, Yu L, Jiang C, Fu X, Liu X, Wang M, et al. Cerebral ischemia increases bone marrow CD4+CD25+FoxP3+ regulatory T cells in mice via signals from sympathetic nervous system. Brain Behav Immun. 2015;43:172-83 pubmed publisher
    ..2-AR antagonist prevented the upregulation of PGE2. PGE2, which acts on prostaglandin E receptor subtype 4 (EP4), upregulated the expression of receptor activator for NF-κB ligand (RANKL) in CD4(+) T cells and mediated the ..
  17. Wu F, Wen Z, Zhi Z, Li Y, Zhou L, Li H, et al. MPGES-1 derived PGE2 inhibits cell migration by regulating ARP2/3 in the pathogenesis of Hirschsprung disease. J Pediatr Surg. 2019;: pubmed publisher
    ..Here we thoroughly inquire the role mPGES-1 derived PGE2 plays in cell migration which might provide a new thinking in the investigation interrelated to the pathogenesis of HSCR. ..
  18. Al Kofahi M, Omura S, Tsunoda I, Sato F, Becker F, Gavins F, et al. IL-1β reduces cardiac lymphatic muscle contraction via COX-2 and PGE2 induction: Potential role in myocarditis. Biomed Pharmacother. 2018;107:1591-1600 pubmed publisher
    ..Using prostaglandin E receptor 4 (EP4) receptor antagonist, we demonstrated that EP4 receptor blockade maintained RCLMC contractility following IL-1β ..
  19. Kimple M, Keller M, Rabaglia M, Pasker R, Neuman J, Truchan N, et al. Prostaglandin E2 receptor, EP3, is induced in diabetic islets and negatively regulates glucose- and hormone-stimulated insulin secretion. Diabetes. 2013;62:1904-12 pubmed publisher
    ..Taken together, our results identify EP3 as a new therapeutic target for β-cell dysfunction in T2D. ..
  20. Shahnazi M, Mohammadi M, Mohaddes G, Latifi Z, Ghasemnejad T, Nouri M, et al. Dietary omega-3 and -6 fatty acids affect the expression of prostaglandin E2 synthesis enzymes and receptors in mice uteri during the window of pre-implantation. Biochem Biophys Res Commun. 2018;503:1754-1760 pubmed publisher
    ..microsomal- and cytosolic- PGE synthase (mPGES and cPGES) and protein expressions of PGE receptor 2 and 4 (EP2 and EP4) were evaluated in uterus tissues of control as well as omega 3 and omega 6 received mice at days 1-5 of pregnancy...
  21. Mieno H, Ueta M, Yamada K, Yamanaka Y, Nakayama T, Watanabe A, et al. Expression of prostaglandin E2 receptor 3 in the eyelid epidermis of patients with Stevens-Johnson syndrome/toxic epidermal necrolysis. Br J Ophthalmol. 2019;: pubmed publisher
    ..Thus, EP3 expression in the epidermis might contribute to a silencing of skin inflammation in chronic-phase SJS/TEN. ..
  22. Chang J, Vacher J, Yao B, Fan X, Zhang B, Harris R, et al. Prostaglandin E receptor 4 (EP4) promotes colonic tumorigenesis. Oncotarget. 2015;6:33500-11 pubmed publisher
    ..Since myeloid cells express high levels of the PGE2 receptor subtype, EP4, we selectively ablated EP4 in myeloid cells and studied adenoma formation in a mouse model of intestinal ..
  23. Morimoto K, Sugimoto Y, Katsuyama M, Oida H, Tsuboi K, Kishi K, et al. Cellular localization of mRNAs for prostaglandin E receptor subtypes in mouse gastrointestinal tract. Am J Physiol. 1997;272:G681-7 pubmed
    ..Expression of EP4 mRNA was moderate in surface epithelial cells of the corpus and in glands from the surface to the base of the ..
  24. Oba K, Hosono K, Amano H, Okizaki S, Ito Y, Shichiri M, et al. Downregulation of the proangiogenic prostaglandin E receptor EP3 and reduced angiogenesis in a mouse model of diabetes mellitus. Biomed Pharmacother. 2014;68:1125-33 pubmed publisher
    ..E receptor subtype EP3 was downregulated in sponge granulation tissues in diabetic mice, whereas EP1, EP2, and EP4 were not...
  25. Kochel T, Reader J, Ma X, Kundu N, Fulton A. Multiple drug resistance-associated protein (MRP4) exports prostaglandin E2 (PGE2) and contributes to metastasis in basal/triple negative breast cancer. Oncotarget. 2017;8:6540-6554 pubmed publisher
    ..pathway members MRP4, the prostaglandin transporter PGT, 15-PGDH (PGE2 metabolism), the prostaglandin E receptor EP4, COX-1, and COX-2 in normal, luminal, and basal breast cancer cell lines...
  26. Yang G, Ren Z, Mei Y. Exposure to 50 Hz magnetic field modulates GABAA currents in cerebellar granule neurons through an EP receptor-mediated PKC pathway. J Cell Mol Med. 2015;19:2413-22 pubmed publisher
    ..by application of DHA or EP1 receptor-specific (prostaglandin E receptor 1) antagonist (SC19220), but not by EP2-EP4 receptor-specific antagonists...
  27. Xu X, Cheng H, Cao J, DU H, Meng Q, Guo M. [Modified Cheng's Juanbi Decoction downregulates expression of prostaglandin E receptor 4 in synovial tissue in rats with adjuvant arthritis]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017;33:736-740 pubmed
    ..Conclusion Cheng's Juanbi Decoction can reduce the level of PTGER4 mRNA in the synovial tissue in AA rats. ..
  28. Yagami T, Koma H, Yamamoto Y. Pathophysiological Roles of Cyclooxygenases and Prostaglandins in the Central Nervous System. Mol Neurobiol. 2016;53:4754-71 pubmed publisher
    ..PGD2, PGE2, and PGI2 exhibit neuroprotective effects via Gs-coupled DP1, EP2/EP4, and IP receptors, respectively. COX-2, PGD2, PGE2, PGF2α, and TXA2 are elevated in stroke...
  29. Colombe L, Michelet J, Bernard B. Prostanoid receptors in anagen human hair follicles. Exp Dermatol. 2008;17:63-72 pubmed
    ..Although extracting a clear functional significance from this intricate network remains open challenge, FP labelling, i.e. could explain the biological effect of PGF(2alpha) on hair regrowth, by directly modulating DP function. ..
  30. Fujikawa R, Higuchi S, Nakatsuji M, Yasui M, Ikedo T, Nagata M, et al. EP4 Receptor-Associated Protein in Microglia Promotes Inflammation in the Brain. Am J Pathol. 2016;186:1982-1988 pubmed publisher
  31. Okumura Y, Yamagishi T, Nukui S, Nakao K. Discovery of AAT-008, a novel, potent, and selective prostaglandin EP4 receptor antagonist. Bioorg Med Chem Lett. 2017;27:1186-1192 pubmed publisher
    ..2, a novel series of para-N-acylaminomethylbenzoic acids was identified and developed as selective prostaglandin EP4 receptor antagonists...
  32. Ohkura N, Edanami N, Takeuchi R, Tohma A, Ohkura M, Yoshiba N, et al. Effects of pulpotomy using mineral trioxide aggregate on prostaglandin transporter and receptors in rat molars. Sci Rep. 2017;7:6870 pubmed publisher
    ..by examining the localisation and mRNA expression levels of its transporter (Pgt) and two of its receptors (Ep2 and Ep4) in a rat model of pulpotomy with MTA capping...
  33. An S, Yang J, Xia M, Goetzl E. Cloning and expression of the EP2 subtype of human receptors for prostaglandin E2. Biochem Biophys Res Commun. 1993;197:263-70 pubmed
    ..That most EP2 receptor mRNA is in lung, kidney, intestinal, glandular and immune tissues, is consistent with functional responses. ..
  34. Kvirkvelia N, Vojnovic I, Warner T, Athie Morales V, Free P, Rayment N, et al. Placentally derived prostaglandin E2 acts via the EP4 receptor to inhibit IL-2-dependent proliferation of CTLL-2 T cells. Clin Exp Immunol. 2002;127:263-9 pubmed
    ..receptors, we have established that the immunosuppressive effect of PGE2 on CTLL-2 cells is exerted via the EP4 receptor...
  35. Schiffler M, Chandrasekhar S, Fisher M, Harvey A, Kuklish S, Wang X, et al. Discovery and characterization of a potent and selective EP4 receptor antagonist. Bioorg Med Chem Lett. 2015;25:3176-8 pubmed publisher
    b>EP4 is a prostaglandin E2 receptor that is a target for potential anti-nociceptive therapy. Described herein is a class of amphoteric EP4 antagonists which reverses PGE2-induced suppression of TNFα production in human whole blood...
  36. Rong Y, Yuan C, Qu Z, Zhou H, Guan Q, Yang N, et al. Doxorubicin resistant cancer cells activate myeloid-derived suppressor cells by releasing PGE2. Sci Rep. 2016;6:23824 pubmed publisher
    ..The secreted PGE2 can stimulate expansion and polymerization of MDSCs by directly target to its receptors, EP2/EP4, on the surface of MDSCs, which consequently triggers production of miR-10a through activating PKA signaling...
  37. Mortimer L, Moreau F, MacDonald J, Chadee K. NLRP3 inflammasome inhibition is disrupted in a group of auto-inflammatory disease CAPS mutations. Nat Immunol. 2016;17:1176-86 pubmed publisher
    ..kinase A (PKA), which was induced by prostaglandin E2 (PGE2) signaling via the PGE2 receptor E-prostanoid 4 (EP4). PKA directly phosphorylated the cytoplasmic receptor NLRP3 and attenuated its ATPase function...
  38. Karger C, Machura K, Schneider A, Hugo C, Todorov V, Kurtz A. COX-2-derived PGE2 triggers hyperplastic renin expression and hyperreninemia in aldosterone synthase-deficient mice. Pflugers Arch. 2018;470:1127-1137 pubmed publisher
    ..renin cells in AS-/- kidneys were found to express the prostaglandin E2 receptors EP2 and EP4. Global deletion of EP2 receptors did not alter renin mRNA nor PRC values in AS-/- mice...
  39. Amre D, Mack D, Morgan K, Israel D, Deslandres C, Seidman E, et al. Susceptibility loci reported in genome-wide association studies are associated with Crohn's disease in Canadian children. Aliment Pharmacol Ther. 2010;31:1186-91 pubmed publisher
    ..07). The ZNF365 and STAT3 SNPs were predominantly associated with ileal disease with or without colonic involvement. The identified susceptibility genes/loci for adult-onset CD also confer risk for paediatric-onset CD. ..
  40. Iimuro Y, Ohashi K, Suzumura K, Hai S, Tanaka S, Nakamura I, et al. Rare form of extraovarian primary peritoneal papillary serous carcinoma with solitary cystic lesion mimicking a liver tumor; report of a case. Clin J Gastroenterol. 2013;6:145-9 pubmed publisher
    ..Immunohistologically, the tumor cells were positive for CA 125 and Ber-EP4 and negative for D2-40 or calretinin, ruling out the possibility of mesothelioma, and the diagnosis of the tumor ..
  41. Zhu J, Mayr D, Kuhn C, Mahner S, Jeschke U, von Schönfeldt V. Prostaglandin E2 receptor EP1 in healthy and diseased human endometrium. Histochem Cell Biol. 2018;149:153-160 pubmed publisher
    ..EP1 may play a role in human endometrial physiology and pathology. Further studies on the effect of EP1 on human endometrium are needed. ..
  42. Majumder M, Nandi P, Omar A, Ugwuagbo K, Lala P. EP4 as a Therapeutic Target for Aggressive Human Breast Cancer. Int J Mol Sci. 2018;19: pubmed publisher
    ..family of GPCR, their physiological and pathological roles in carcinogenesis, with special emphasis on the roles of EP4 in breast cancer progression...
  43. Desai S, April H, Nwaneshiudu C, Ashby B. Comparison of agonist-induced internalization of the human EP2 and EP4 prostaglandin receptors: role of the carboxyl terminus in EP4 receptor sequestration. Mol Pharmacol. 2000;58:1279-86 pubmed
    ..couples to stimulation of adenylyl cyclase through two distinct G protein-coupled receptors designated EP2 and EP4. Although they have similar affinities for PGE(2), the EP(2) and EP4 receptors have distinct structural ..
  44. Park B, Park S, Park J, Uh S, Choi J, Kim Y, et al. Association of PTGER gene family polymorphisms with aspirin intolerant asthma in Korean asthmatics. BMB Rep. 2010;43:445-9 pubmed
    ..Our findings provide further evidence that polymorphisms in PTGER3 might play a significant role in aspirin hypersensitivity among Korean asthmatics. ..
  45. Grilo A, Sáez Rosas M, Santos Morano J, Sanchez E, Moreno Rey C, Real L, et al. Identification of genetic factors associated with susceptibility to angiotensin-converting enzyme inhibitors-induced cough. Pharmacogenet Genomics. 2011;21:10-7 pubmed publisher
    ..384 for protective combinations and 2.732?OR?7.216 for risk combinations). These results are consistent with the hypothesis that the mechanism of cough is related to the accumulation of bradykinin, substance P, and prostaglandins. ..
  46. Deacon K, Knox A. Human airway smooth muscle cells secrete amphiregulin via bradykinin/COX-2/PGE2, inducing COX-2, CXCL8, and VEGF expression in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2015;309:L237-49 pubmed publisher
    ..a mechanism dependent on BK-induced COX-2 expression, increased PGE2 output, and the stimulation of HASMC EP2 and EP4 receptors...
  47. Torday J, Rehan V. On the evolution of the pulmonary alveolar lipofibroblast. Exp Cell Res. 2016;340:215-9 pubmed publisher
    ..Moreover, such detailed knowledge of the workings of the lipofibroblast have provided insight to the etiology and effective treatment of Bronchopulmonary Dysplasia based on physiologic principles rather than on pharmacology. ..
  48. 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 ..
  49. Satitsri S, Pongkorpsakol P, Srimanote P, Chatsudthipong V, Muanprasat C. Pathophysiological mechanisms of diarrhea caused by the Vibrio cholerae O1 El Tor variant: an in vivo study in mice. Virulence. 2016;7:789-805 pubmed publisher
    ..Furthermore, EP2 and EP4 PGE2 receptor antagonists ameliorated the fluid secretion in the infected ileal loops...
  50. 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 ..
  51. Schober L, Khandoga A, Dwivedi S, Penz S, Maruyama T, Brandl R, et al. The role of PGE(2) in human atherosclerotic plaque on platelet EP(3) and EP(4) receptor activation and platelet function in whole blood. J Thromb Thrombolysis. 2011;32:158-66 pubmed publisher
    ..We conclude that PGE(2) in human atherosclerotic lesions does not modulate (i.e. stimulate or inhibit) atherothrombosis in blood after plaque rupture. ..
  52. Allison S, Petrovic N, Mackenzie P, Murray M. Pro-migratory actions of the prostacyclin receptor in human breast cancer cells that over-express cyclooxygenase-2. Biochem Pharmacol. 2015;96:306-14 pubmed publisher
    ..In further studies, the prostacyclin/IP receptor and PGE2/EP4 receptor pathways were found to be functionally independent and the inhibition of phosphatidylinositol 3-kinase (..
  53. Wang F, Lu X, Peng K, Fang H, Zhou L, Su J, et al. Antidiuretic Action of Collecting Duct (Pro)Renin Receptor Downstream of Vasopressin and PGE2 Receptor EP4. J Am Soc Nephrol. 2016;27:3022-3034 pubmed
    ..Together, these results suggest a previously undescribed linear AVP/PGE2/EP4/PRR pathway in the CD for regulation of AQP2 expression and urine concentrating capability. ..
  54. Laporte M, Weems Y, Arreguin Arevalo A, Nett T, Tsutahara N, Sy T, et al. Effects of LPA2R, LPA3R, or EP4R agonists on luteal or endometrial function in vivo or in vitro and sirtuin or EP1R, EP2R, EP3R or EP4R agonists on endometrial secretion of PGE and PGF2αin vitro. Theriogenology. 2017;95:8-17 pubmed publisher
    ..An EP4R and lysophosphatidic acid (LPA) LPA2R and LPA3R agonists were reported to inhibit luteal function and sirtuins have ..
  55. Rodríguez Lagunas M, Martín Venegas R, Moreno J, Ferrer R. PGE2 promotes Ca2+-mediated epithelial barrier disruption through EP1 and EP4 receptors in Caco-2 cell monolayers. Am J Physiol Cell Physiol. 2010;299:C324-34 pubmed publisher
  56. Dey I, Beck P, Chadee K. Lymphocytic colitis is associated with increased pro-inflammatory cytokine profile and up regulation of prostaglandin receptor EP4. PLoS ONE. 2013;8:e61891 pubmed publisher
    ..Recent genome wide screens have found an association between prostaglandin receptor EP4 expression and inflammatory bowel disease; however, EP4 expression has never been studied in MC...
  57. Nasrallah R, Hassouneh R, Zimpelmann J, Karam A, Thibodeau J, Burger D, et al. Prostaglandin E2 increases proximal tubule fluid reabsorption, and modulates cultured proximal tubule cell responses via EP1 and EP4 receptors. Lab Invest. 2015;95:1044-55 pubmed publisher
    ..EP1 and EP4 were detected in MCT, but EP2 and EP3 are not expressed...
  58. Chen Y, Tang Q, Wu J, Zheng F, Yang L, Hann S. Inactivation of PI3-K/Akt and reduction of SP1 and p65 expression increase the effect of solamargine on suppressing EP4 expression in human lung cancer cells. J Exp Clin Cancer Res. 2015;34:154 pubmed publisher
    ..The prostaglandin E2 receptor EP4 is highly expressed in human cancer, however, the functional role of EP4 in the occurrence and progression of non ..
  59. Maślanka T, Chrostowska M, Otrocka Domagała I, Snarska A, Mikiewicz M, Zuśka Prot M, et al. Prostaglandin E2 exerts the proapoptotic and antiproliferative effects on bovine NK cells. Res Vet Sci. 2016;107:80-87 pubmed publisher
    ..The blockade of EP1, EP2, EP3 and EP4 receptors did not prevent the PGE2-induced apoptosis and depletion of NK cells...
  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
    ..Our results demonstrate a mechanism by which WAE cells are formed by PGE2 and suggest a process of adaptive cellular reprogramming of the intestinal epithelium that occurs to ensure proper repair to injury. ..
  61. Parga J, García Garrote M, Martinez S, Raya A, Labandeira Garcia J, Rodriguez Pallares J. Prostaglandin EP2 Receptors Mediate Mesenchymal Stromal Cell-Neuroprotective Effects on Dopaminergic Neurons. Mol Neurobiol. 2018;55:4763-4776 pubmed publisher
    ..Taken together, our results demonstrate for the first time the involvement of prostaglandin signaling from MSC in dopaminergic neuron survival through EP2 receptors, and suggest new approaches for treatment of Parkinson's disease. ..
  62. Taniguchi S, Watanabe T, Nakao A, Seki G, Uwatoko S, Kurokawa K. Detection and quantitation of EP3 prostaglandin E2 receptor mRNA along mouse nephron segments by RT-PCR. Am J Physiol. 1994;266:C1453-8 pubmed
    ..The results support the notion that PGE2 modulates water and solute transport through the EP3 receptor in specific structures of the kidney...
  63. Bradbury D, Newton R, Zhu Y, El Haroun H, Corbett L, Knox A. Cyclooxygenase-2 induction by bradykinin in human pulmonary artery smooth muscle cells is mediated by the cyclic AMP response element through a novel autocrine loop involving endogenous prostaglandin E2, E-prostanoid 2 (EP2), and EP4 receptors. J Biol Chem. 2003;278:49954-64 pubmed
    ..Exogenous PGE2 and EP2 (ONO-AE1 259) and EP4 (ONO-AE1 329) PGE2 receptor agonists mimicked the effect of BK...
  64. Sarrazin P, Hackett J, Fortier I, Gallant M, de Brum Fernandes A. Role of EP3 and EP4 prostaglandin receptors in reorganization of the cytoskeleton in mature human osteoclasts. J Rheumatol. 2004;31:1598-606 pubmed
    ..In situ hybridization and immunohistochemistry were used to detect the presence of EP1, EP2, EP3, and EP4 receptors on these cells...
  65. Muller M, Sales K, Katz A, Jabbour H. Seminal plasma promotes the expression of tumorigenic and angiogenic genes in cervical adenocarcinoma cells via the E-series prostanoid 4 receptor. Endocrinology. 2006;147:3356-65 pubmed
    ..mediating the role of seminal plasma and PGE(2) in the regulation of tumorigenic and angiogenic genes via the EP4 receptor in cervical adenocarcinoma (HeLa) cells...
  66. Hoshino T, Namba T, Takehara M, Nakaya T, Sugimoto Y, Araki W, et al. Prostaglandin E2 stimulates the production of amyloid-beta peptides through internalization of the EP4 receptor. J Biol Chem. 2009;284:18493-502 pubmed publisher
  67. Filipenko I, Schwalm S, Reali L, Pfeilschifter J, Fabbro D, Huwiler A, et al. Upregulation of the S1P3 receptor in metastatic breast cancer cells increases migration and invasion by induction of PGE2 and EP2/EP4 activation. Biochim Biophys Acta. 2016;1861:1840-1851 pubmed publisher
  68. Fujikawa R, Higuchi S, Ikedo T, Nagata M, Hayashi K, Yang T, et al. Behavioral abnormalities and reduced norepinephrine in EP4 receptor-associated protein (EPRAP)-deficient mice. Biochem Biophys Res Commun. 2017;486:584-588 pubmed publisher
    b>EP4 receptor-associated protein (EPRAP) is a newly identified molecule that regulates macrophage activation...
  69. Salinas Parra N, Reyes Martínez C, Prieto M, Gonzalez A. Prostaglandin E2 Induces Prorenin-Dependent Activation of (Pro)renin Receptor and Upregulation of Cyclooxygenase-2 in Collecting Duct Cells. Am J Med Sci. 2017;354:310-318 pubmed publisher
    ..CD cells express EP1 and EP4, which are linked to protein kinase C (PKC) and PKA downstream pathways, respectively...
  70. Kaya D, Gram A, Kowalewski M, Schäfer Somi S, Kuru M, Boos A, et al. Expression of GnRH receptor in the canine corpus luteum, and luteal function following deslorelin acetate-induced puberty delay. Reprod Domest Anim. 2017;52:1104-1112 pubmed publisher
    ..P4)-receptor (PGR), prolactin receptor (PRLR), PGE2-synthase (PTGES) and PGE2 receptors (PTGER2/EP2, PTGER4/EP4), vascular endothelial growth factor (VEGFA) and VEGF receptors (VEGFR1 and VEGFR2), cyclooxygenase 2 (COX2/PTGS2), ..
  71. Tang Q, Zheng F, Wu J, Xiao Q, Li L, Hann S. Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1. Cell Physiol Biochem. 2017;43:2310-2326 pubmed publisher
    ..the growth of non-small-cell lung cancer (NSCLC) cells through suppression of prostaglandin E2 (PGE2) receptor EP4 gene and regulation of downstream signaling pathways...
  72. Neuschäfer Rube F, Hermosilla R, Rehwald M, Ronnstrand L, Schulein R, Wernstedt C, et al. Identification of a Ser/Thr cluster in the C-terminal domain of the human prostaglandin receptor EP4 that is essential for agonist-induced beta-arrestin1 recruitment but differs from the apparent principal phosphorylation site. Biochem J. 2004;379:573-85 pubmed
    hEP4-R (human prostaglandin E2 receptor, subtype EP4) is a G(s)-linked heterotrimeric GPCR (G-protein-coupled receptor)...
  73. Park H, Shin E, Lee J, Kim S, Kim S, Chang Y, et al. Association between genetic variations in prostaglandin E2 receptor subtype EP3 gene (Ptger3) and asthma in the Korean population. Clin Exp Allergy. 2007;37:1609-15 pubmed
    ..The present study demonstrated that genetic variations in Ptger3 are significantly associated with the risk and severity of asthma in the Korean population. ..
  74. Doherty G, Byrne S, Molloy E, Malhotra V, Austin S, Kay E, et al. Proneoplastic effects of PGE2 mediated by EP4 receptor in colorectal cancer. BMC Cancer. 2009;9:207 pubmed publisher
    ..Immunohistochemistry was employed for expression studies on formalin fixed paraffin embedded tumour tissue. EP4 was the most abundant subtype of PGE2 receptor in HT-29 and HCA7 cells (which show COX-2 dependent PGE2 generation) ..
  75. Philipose S, Konya V, Sreckovic I, Marsche G, Lippe I, Peskar B, et al. The prostaglandin E2 receptor EP4 is expressed by human platelets and potently inhibits platelet aggregation and thrombus formation. Arterioscler Thromb Vasc Biol. 2010;30:2416-23 pubmed publisher
    ..are mediated through 4 G protein-coupled receptors, termed E-type prostaglindin (EP) receptor EP1, EP2, EP3, and EP4. The platelet-stimulating effect of PGE(2) has been suggested to involve EP3 receptors...
  76. Chandramouli A, Onyeagucha B, Mercado Pimentel M, Stankova L, Shahin N, Lafleur B, et al. MicroRNA-101 (miR-101) post-transcriptionally regulates the expression of EP4 receptor in colon cancers. Cancer Biol Ther. 2012;13:175-83 pubmed publisher
    Expression of the PGE2 receptor, EP4, is up-regulated during colorectal carcinogenesis. However the mechanism leading to deregulation of the EP4 receptor is not known...
  77. Zschockelt L, Amelkina O, Siemieniuch M, Kowalewski M, Dehnhard M, Jewgenow K, et al. Synthesis and reception of prostaglandins in corpora lutea of domestic cat and lynx. Reproduction. 2016;152:111-26 pubmed publisher
    ..In contrast, expression of PTGFR was evident in nearly all investigated CL of cat and lynxes, implying that luteal regression, e.g. at the end of pregnancy, is triggered by extra-luteal PGF2?. ..
  78. Tewhey R, Kotliar D, Park D, Liu B, Winnicki S, Reilly S, et al. Direct Identification of Hundreds of Expression-Modulating Variants using a Multiplexed Reporter Assay. Cell. 2016;165:1519-1529 pubmed publisher
    ..spondylitis, and provide direct evidence of a non-coding variant that alters expression of the prostaglandin EP4 receptor...
  79. Liang L, Zhang Q, Luo L, Yue J, Zhao Y, Han M, et al. Polymorphisms in the prostaglandin receptor EP2 gene confers susceptibility to tuberculosis. Infect Genet Evol. 2016;46:23-27 pubmed publisher
    ..PGE2 modulates a variety of immune functions via four receptors (EP1-EP4), which mediate distinct PGE2 effects...
  80. Ackerman J, Best K, O Keefe R, Loiselle A. Deletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing. Sci Rep. 2017;7:8658 pubmed publisher
    ..In the present study we tested the hypothesis that deletion of the PGE2 receptor EP4 in S100a4-lineage cells would decrease adhesion formation...
  81. Araki Y, Suganami A, Endo S, Masuda Y, Fukushima K, Regan J, et al. PGE1 and E3 show lower efficacies than E2 to ?-catenin-mediated activity as biased ligands of EP4 prostanoid receptors. FEBS Lett. 2017;: pubmed publisher
    ..These results provide a plausible reason why PGE1 and PGE3 function as anti-cancer prostanoids as a result of novel biased activity for EP4 receptors.
  82. Theodoridis A, Prechtel A, Turza N, Zenke M, Steinkasserer A. Infection of human dendritic cells with herpes simplex virus type 1 dramatically diminishes the mRNA levels of the prostaglandin E(2) receptors EP2 and EP4. Immunobiology. 2007;212:827-38 pubmed
    ..migration of DCs and exerts its effects via prostaglandin E(2) receptor 2 (EP2) and prostaglandin E(2) receptor 4 (EP4)...
  83. Luschnig Schratl P, Sturm E, Konya V, Philipose S, Marsche G, Fröhlich E, et al. EP4 receptor stimulation down-regulates human eosinophil function. Cell Mol Life Sci. 2011;68:3573-87 pubmed publisher
    ..Here we observed that a selective agonist of the PGE(2) receptor EP4, ONO AE1-329, potently attenuated the chemotaxis of human peripheral blood eosinophils, upregulation of the ..
  84. Catalano R, Wilson M, Boddy S, McKinlay A, Sales K, Jabbour H. Hypoxia and prostaglandin E receptor 4 signalling pathways synergise to promote endometrial adenocarcinoma cell proliferation and tumour growth. PLoS ONE. 2011;6:e19209 pubmed publisher
    ..Finally we have shown that PGE(2) and hypoxia synergise to promote cellular proliferation of endometrial adenocarcinoma cells. ..
  85. Galea G, Sunters A, Meakin L, Zaman G, Sugiyama T, Lanyon L, et al. Sost down-regulation by mechanical strain in human osteoblastic cells involves PGE2 signaling via EP4. FEBS Lett. 2011;585:2450-4 pubmed publisher
    ..Strain-induced Sost down-regulation was recapitulated by cyclo-oxygenase-2-mediated PGE2, acting through the EP4 receptor, whereas strain-related up-regulation of osteocalcin was mediated by the EP2 receptor...
  86. Shin J, Park I, Moon Y, Hong S, Cho J, Um J, et al. Inhibitory effect of prostaglandin E(2) on the migration of nasal fibroblasts. Am J Rhinol Allergy. 2014;28:e120-4 pubmed publisher
    ..Reverse-transcription polymerase chain reaction was performed for E prostanoid (EP) 1, EP2, EP3, and EP4 receptors. EP receptor-selective agonists and antagonists were used to evaluate receptor functions...
  87. Majumder M, Landman E, Liu L, Hess D, Lala P. COX-2 Elevates Oncogenic miR-526b in Breast Cancer by EP4 Activation. Mol Cancer Res. 2015;13:1022-33 pubmed publisher
    ..mechanisms, including induction of stem-like cells (SLC), owing to activation of the prostaglandin E2 receptor EP4 (PTGER4). COX-2 overexpression also upregulated microRNA-526b (miR-526b), in association with aggressive phenotype...
  88. Rodriguez Rodriguez L, Ivorra Cortes J, Carmona F, Martín J, Balsa A, van Steenbergen H, et al. PTGER4 gene variant rs76523431 is a candidate risk factor for radiological joint damage in rheumatoid arthritis patients: a genetic study of six cohorts. Arthritis Res Ther. 2015;17:306 pubmed publisher
    ..05-1.14, p = 2.10 × 10(-5)), meaning that radiographic yearly progression was 10 % greater for each copy of the minor allele. The PTGER4 gene is a candidate risk factor for radiological progression in RA. ..
  89. Ke J, Yang Y, Che Q, Jiang F, Wang H, Chen Z, et al. Prostaglandin E2 (PGE2) promotes proliferation and invasion by enhancing SUMO-1 activity via EP4 receptor in endometrial cancer. Tumour Biol. 2016;37:12203-12211 pubmed
    ..PGE2 stimulation enhanced the expression of SUMO-1, via PGE2 receptor subtype 4 (EP4). Further analysis implicated the Wnt/?-catenin signaling pathway function as the major mediator of EP4 and SUMO-1...
  90. Pradhan S, Salinas K, Garduno A, Johansson J, Wang Q, MANNING BOG A, et al. Anti-Inflammatory and Neuroprotective Effects of PGE2 EP4 Signaling in Models of Parkinson's Disease. J Neuroimmune Pharmacol. 2017;12:292-304 pubmed publisher
    ..We have previously shown that the prostaglandin PGE2 receptor EP4 suppresses innate immune responses in models of systemic inflammation...
  91. Matsubara S, Shiraishi A, Sakai T, Okuda T, Satake H. Heterodimerization of the prostaglandin E2 receptor EP2 and the calcitonin receptor CTR. PLoS ONE. 2017;12:e0187711 pubmed publisher
    ..Altogether, the present study suggests that a novel GPCR heterodimer, EP2-CTR, is involved in some functional regulation, and paves the way for investigation of novel biological roles of CTR and EP2 in various tissues. ..
  92. Miao J, Lu X, Hu Y, Piao C, Wu X, Liu X, et al. Prostaglandin E2 and PD-1 mediated inhibition of antitumor CTL responses in the human tumor microenvironment. Oncotarget. 2017;8:89802-89810 pubmed publisher
    ..The disruption of COX2/PGE2 signaling using COX2 inhibitors or PGE2 receptors EP2 and EP4 antagonists, combined with anti-PD-1 blockade was therapeutic in terms of improving eradication of tumors and ..