In a previous genome-wide association study of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) patients we reported the association between SJS/TEN and the prostaglandin E receptor 3 (PTGER3) gene, and that its protein PGE<sub>2</sub> receptor 3 (EP3) was markedly downregulated in the conjunctival epithelium of SJS/TEN patients.
Single nucleotide polymorphism association analysis showed that the Toll-like receptor 3 (TLR3), prostaglandin-E receptor 3 (PTGER3), and IKZF1 gene were significantly associated with CM-SJS/TEN with SOC and that they could regulate mucocutaneous inflammation including that of the ocular surface.
We found that levels of prostaglandin-endoperoxide synthase 1 (PTGS1; aka COX-1) and prostaglandin-endoperoxide receptor 3 (PTGER3) mRNA are increased, and levels of prostaglandin-endoperoxide synthase 2 (PTGS2; aka COX-2) mRNA are decreased, in older subjects with schizophrenia (> 40years of age) compared to matched normal controls or younger subjects with schizophrenia (< 40years of age).
In a previous genome-wide association study of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) patients we reported the association between SJS/TEN and the prostaglandin E receptor 3 (PTGER3) gene, and that its protein PGE<sub>2</sub> receptor 3 (EP3) was markedly downregulated in the conjunctival epithelium of SJS/TEN patients.
Through association analyses studies of the 32 single nucleotide polymorphisms, the following single nucleotide polymorphisms were found to have significant associations with the aspirin-intolerant asthma phenotype: -616C>G (P=0.038) and -166G>A (P=0.023) in PTGER2; -1709T>A (P=0.043) in PTGER3; -1254A>G (P=0.018) in PTGER4; 1915T>C (P=0.015) in PTGIR; and -4684C>T (P=0.027), and 795T>C (P=0.032) in TBXA2R.
In the present study, human colon cancer HCA-7 cells were used as a model system to understand the potential role of EP3 receptors in tumor cell migration.
Thus, our study provides strong evidence that selective activation of each of the three variants of the EP3 receptor suppresses tumor cell function by activating a G(12)-RhoA pathway.
Given the known involvement of VEGFR-1 in cellular migration, our results suggest that EP3 receptors may contribute to tumor cell metastasis by increasing cellular migration through the up-regulation of VEGFR-1 signaling.
An association between higher tumoral expression of PTGER3 and shorter patient survival in the ovarian cancer dataset of The Cancer Genome Atlas prompted investigation of the antitumor effects of PTGER3 downmodulation.
Almost all tested plants upregulated the expression of the prostaglandin E receptor 3 gene (PTGER3) suggesting their potential benefits in the treatment of cancer.
Two hundred eighty-nine sporadic breast cancer samples without primary distant metastasis were immunohistochemically analyzed for EP3 receptor expression.
Given the known involvement of VEGFR-1 in cellular migration, our results suggest that EP3 receptors may contribute to tumor cell metastasis by increasing cellular migration through the up-regulation of VEGFR-1 signaling.
We propose, therefore, that the EP3 receptor provides endogenous pain control and that selective activation of EP3 receptors may be a unique approach to reverse inflammatory pain.
Our findings identify the PGE(2) EP3 receptor as a novel proinflammatory, proamyloidogenic, and synaptotoxic signaling pathway, and suggest a role for COX-PGE(2) -EP3 signaling in the development of AD.
In summary, the building up of PGE<sub>2</sub> during the progression of AD leads to specific impairment of hippocampal presynaptic plasticity and highlights EP3 receptors as a potential target to alleviate cognitive deficits in AD.
Mice lacking the EP3 receptor (EP3R) for PGE(2) exhibited fewer apneas and sustained brainstem respiratory activity, demonstrating that PGE(2) exerts its respiratory effects via EP3R.
Consistency of effects between rs7030789 and rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent clinic-based cohorts.Novel genetic loci for apnea phenotypes were identified through the use of customized gene chips and meta-analyses of cohort data with replication in clinic-based samples.