Localization of prostaglandin E2 synthases and E-prostanoid receptors in the spinal cord in a rat model of neuropathic pain

Kanda, Hirosato; Kobayashi, Kimiko; Yamanaka, Hiroki; Okubo, Masamichi; Dai, Yi; Noguchi, Koichi

doi:10.1016/j.brainres.2020.147153

Cited by 10 publications

(5 citation statements)

References 33 publications

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“…In vivo, three primary enzymes-membrane prostaglandin E2 synthase (mPGES)-1, mPGES-2, and cytosolic prostaglandin E2 synthase (cPGES)-are responsible for the production of PGE2 [27,28]. In pathological states such as inflammation, discomfort, and fever, mPGES-1 is the main producer of PGE2 [29].…”

Section: Discussionmentioning

confidence: 99%

PGE2 binding to EP2 promotes ureteral stone expulsion by relaxing ureter via the cAMP-PKA pathway

Su,

Zhou,

Chen

et al. 2024

BMC Urol

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Background This study investigated the relaxation effect of PGE2 on the ureter and its role in promoting calculi expulsion following calculi development. Methods By using immunofluorescence and Western blot, we were able to locate EP receptors in the ureter. In vitro experiments assessed the impact of PGE2, receptor antagonists, and agonists on ureteral relaxation rate. We constructed a model of ureteral calculi with flowable resin and collected ureteral tissue from postoperative side of the ureter after obstruction surgery. Western blot analysis was used to determine the protein expression levels of EP receptors and the PGE2 terminal synthase mPGES-1. Additionally, PGE2 was added to smooth muscle cells to observe downstream cAMP and PKA changes. Results The expression of EP2 and EP4 proteins in ureteral smooth muscle was verified by Western blot analysis. According to immunofluorescence, EP2 was primarily found on the cell membrane, while EP4 was found in the nucleus. In vitro, PGE2 induced concentration-dependent ureteral relaxation. Maximum diastolic rate was 70.94 ± 4.57% at a concentration of 30µM. EP2 antagonists hindered this effect, while EP4 antagonists did not. Obstructed ureters exhibited elevated mPGES-1 and EP2 protein expression (P < 0.01). Smooth muscle cells treated with PGE2 displayed increased cAMP and phosphorylated PKA. Conclusions PGE2 binding to EP2 induces ureteral relaxation through the cAMP-PKA pathway. This will provide a new theoretical basis for the development of new therapeutic approaches for the use of PGE2 in the treatment of ureteral stones.

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Section: Discussionmentioning

confidence: 99%

PGE2 binding to EP2 promotes ureteral stone expulsion by relaxing ureter via the cAMP-PKA pathway

Su,

Zhou,

Chen

et al. 2024

BMC Urol

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“…The discovery of a correlation between POM121L1P and type 2 diabetes mellitus (T2DM) has been reported ( 23 ). PTGES is the terminal enzyme in the biosynthetic process of prostaglandin E2 (PGE2); PTGES could also respond to the stimulation brought by inflammation through a method of catalyzing the conversion of prostaglandin endoperoxide H2 (PGH2) to PGE2, and act as a core regulator in inflammation response ( 24 ), fever ( 25 ), and pain ( 26 , 27 ). In addition, PTGES has also been found to be associated with T2DM.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers associated with immune scores in diabetic retinopathy

Zhang,

Zhu,

Wang

et al. 2023

Front. Endocrinol.

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BackgroundDiabetic retinopathy (DR) causes irreversible visual impairment in diabetes mellitus (DM) patients. Immunity played a crucial role in DR. Nevertheless, the triggering mechanism of DR was not yet thorough enough. Herein, we aim to identify the immune-associated genes as biomarkers associated with immune scores that can distinguish early DR from DM without DR.MethodsIn this study, total RNA of peripheral blood mononuclear cell (PBMC) samples from 15 non-proliferative DR patients and 15 DM patients without DR were collected and the transcriptome sequencing data were extracted. Firstly, the target genes were obtained by intersecting the differentially expressed genes (DEGs), which were screened by “limma”, and the module genes (related to immune scores), which were screened by “WGCNA”. In order to screen for the crucial genes, three machine learning algorithms were implemented, and a receiver operating characteristic (ROC) curve was used to obtain the diagnostic genes. Moreover, the gene set enrichment analysis (GSEA) was performed to understand the function of diagnostic genes, and analysis of the proportions of immune cells and their association with diagnostic genes was performed to analyze the pathogenesis of DR. Furthermore, the regulatory network of TF–mRNA–miRNA was built to reveal the possible regulation of diagnostic genes. Finally, the quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the mRNA level of diagnostic genes.ResultsA total of three immune-associated diagnostic genes, namely, FAM209B, POM121L1P, and PTGES, were obtained, and their expression was increased in PBMC samples of DR, and qRT-PCR results confirmed these results. Moreover, the functions of these genes were associated with immune response. The expression of POM121L1P and PTGES was significantly negatively associated with naive B cells, and the expression of FAM209B was significantly negatively associated with immature dendritic cells. Moreover, ESR1 could regulate both FAM209B and PTGES.ConclusionThis study identified three immune-associated diagnostic genes, FAM209B, POM121L1P, and PTGES, as biomarkers associated with immune scores in DR for the first time. This finding might proffer a novel perspective of the triggering mechanism of DR, and help to understand the role of immune-associated genes in the molecular mechanism of DR more deeply.

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“…ISHH was performed as described previously. (14,16) For ISHH, clones (pCRII-TOPO, Invitrogen Corp., Carlsbad, CA) containing a partial sequence corresponding to the coding regions of EP1, EP2, EP3, EP4, COX-1, COX-2, mPGES-1, and mPGES-2, and cPGES were prepared (Table 1). In brief, 35S-labeled RNA probes for PGE 2 synthases and EP receptors were prepared by in vitro transcription using T7 or SP6 RNA polymerase.…”

Section: Methodsmentioning

confidence: 99%

Acid increases PGE<sub>2</sub> in the duodenal mucosa in rats

Fujimura

Kondo

Kobayashi

et al. 2022

J. Clin. Biochem. Nutr.

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Attention has recently been paid to the duodenum as the pathophysiologic center of functional dyspepsia. However, the precise mechanisms of symptom generation remain unknown. We here investigated the effect of acid on duodenal prostaglandin E 2 and localization of prostaglandin E 2 related receptors. Sprague-Dawley rats were used for this study. Hydrochloric acid was administered in the duodenum, then prostaglandin E 2 levels in the duodenum were measured using the ELISA. The expression and localization of prostaglandin receptors (EP1-4) and the mRNAs of prostaglandin synthases were investigated using in situ hybridization histochemistry in duodenal tissue. After acid perfusion, prostaglandin E 2 levels in the duodenum significantly increased. EP3 was expressed mainly at the myenteric plexus in the duodenal mucosa, and EP4 at both the epithelial surface and myenteric plexus. Contrary, EP2 was sparsely distributed in the villi and EP1 were not clearly seen on in situ hybridization histochemistry. Prostaglandin-synthetic enzymes were also distributed in the duodenal mucosa. The prostaglandin E 2 levels in the duodenum increased after acidification. Prostaglandin E 2 receptors and prostaglandin E 2 -producing enzymes were both observed in rat duodenum. These observations suggest that duodenal prostaglandin E 2 possibly play a role in the symptom generation of functional dyspepsia.

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Localization of prostaglandin E2 synthases and E-prostanoid receptors in the spinal cord in a rat model of neuropathic pain

Cited by 10 publications

References 33 publications

PGE2 binding to EP2 promotes ureteral stone expulsion by relaxing ureter via the cAMP-PKA pathway

PGE2 binding to EP2 promotes ureteral stone expulsion by relaxing ureter via the cAMP-PKA pathway

Identification of biomarkers associated with immune scores in diabetic retinopathy

Acid increases PGE<sub>2</sub> in the duodenal mucosa in rats

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