These findings indicate that COX-1 and the EP1 and EP3 receptors mediate the downstream pathological effects of PGE<sub>2</sub> during polymicrobial IAI and may serve as effective therapeutic targets.
Thus, the PGE<sub>2</sub>/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6C<sup>low</sup> Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.
We found elevated expression of PTGES2 and PTGER4 and suppression of PTGER1 and PTGER3 in endometrial adenocarcinomas compared with normal endometrium.
When receptor expression was quantitated by densitometry, immunoreactive EP3 protein on deep basolateral (but not other) FAP crypt epithelium was enhanced 2.8-fold over normal, and the number of prostanoid receptor EP4+ mononuclear cells by 2.5-fold.
These findings indicate that the EP3 receptor activated by PGE(2) may couple to Gs protein and activate cyclic AMP (cAMP)-PKA, downregulating the levels of JTV1 protein, consequently inhibiting the ubiquitination of FBP1 and increasing FBP1 protein expression, thus promoting liver cancer cell growth.
However, the functions and the mechanisms of those splice variants of EP3 receptors in promoting liver cancer cell growth and invasion remain to be elucidated.
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.
Since PGE2 has been shown to have important pathophysiological roles in ALS, experiments were performed to identify EP3 receptor isoform(s) in spinal motor neurons of wild-type (WT) and ALS model (G93A) mice.
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.
These results suggest that down-regulation of EP3 expression by oxLDL is associated with impairment of EP3-mediated anti-inflammatory effects, and that EP3 receptor activity may exert a beneficial effect on atherosclerosis.
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.
These results suggest that down-regulation of EP3 expression by oxLDL is associated with impairment of EP3-mediated anti-inflammatory effects, and that EP3 receptor activity may exert a beneficial effect on atherosclerosis.
However, the functional aspects of EP3 receptor in breast cancer and the way how EP3 may oppose the pro-tumorigenic effects of PGE2 elevation and COX-2 overexpression are not fully understood so far.
Additionally, EP3 (PTGER3) transcript levels were significantly decreased in human prostate cancer tissues compared with those in normal human prostate tissues, suggesting that EP3 is important to prostate carcinogenesis.
Given the cardiovascular hazard of a COX-2 inhibitor, our findings indicate that the EP3 receptor and its downstream pathways may be potential targets for prevention of TCDD-associated cardiovascular diseases.
Little is known about the expression of the Prostaglandin E receptor type 3 (EP3) or the Prostaglandin (PG)E₂-EP3 signalling in cervical cancer, so the aim of the study was to analyse the expression of the EP3 receptor in cervical cancer and find prognostic factors in relation to survival; EP3 immunohistological staining of 250 cervical cancer slides was performed and analysed with a semi-quantitative score.