Ask about this productRelated genes to: PTGES2 antibody
- Gene:
- PTGES2 NIH gene
- Name:
- prostaglandin E synthase 2
- Previous symbol:
- C9orf15
- Synonyms:
- FLJ14038
- Chromosome:
- 9q34.11
- Locus Type:
- gene with protein product
- Date approved:
- 2002-01-29
- Date modifiied:
- 2016-10-05
Related products to: PTGES2 antibody
Related articles to: PTGES2 antibody
- With the increasing trend of delayed childbearing, the decline in oocyte quality associated with advanced maternal age has emerged as a pressing concern. However, the mechanism remains unclear, and effective strategies for improvement are currently lacking. Previously, we reported that the downregulation of the mevalonate pathway in aged granulosa cells (GCs) contributed to meiotic defects in oocytes, which may implicate farnesyl pyrophosphate-mediated protein farnesylation. Nevertheless, the role of farnesylation in ovarian aging and its impact on oocytes requires further investigation. In this study, using cumulus-oocyte complexes (COCs) from young and aged female mice, we observed impaired cumulus expansion and concurrent meiotic defects during aged oocyte maturation, accompanied by significantly reduced protein farnesylation in aged GCs. Furthermore, inhibiting farnesylation with FTI-277 in young COCs recapitulated the aging phenotype, disrupting cumulus expansion and inducing meiotic defects similar to those in aged COCs. Conversely, restoring farnesylation via farnesol supplementation effectively ameliorated these deficits in both aged COCs (in vitro) and aged mice (in vivo). Proteomic analysis and experimental validation identified prostaglandin E2 synthase 2 (PTGES2) as a farnesylated protein. Mechanistically, age-related decline in PTGES2 farnesylation in GCs reduces its endoplasmic reticulum localization and impairs prostaglandin E2 (PGE2) production, thereby compromising PGE2-dependent cumulus expansion and oocyte maturation. Collectively, our findings highlight the detrimental effects of decreased farnesylation in aged GCs on oocyte quality and propose a potential therapeutic strategy for improving the developmental competence of aged oocytes. - Source: PubMed
Zhang SainanQi JiahuiLiu ChuanmingZhang HuidanGuo BichunWu DieLiu YicenZhen XinZhang YangKang NannanZhou JidongYan GuijunLi ChaojunDing LijunSun Haixiang - The endocannabinoid system regulates key biological functions such as neuroprotection, pain modulation, inflammation, and immunomodulation. Cannabis-based therapies have gained attention due to the therapeutic potential of their bioactive compounds, particularly phytocannabinoids like cannabidiol (CBD), which exhibit anti-inflammatory, neuroprotective, and immunomodulatory properties. Mesenchymal stem cells (MSCs) are widely studied for their regenerative and immunomodulatory potential. This study evaluated the effects of priming canine adipose tissue-derived MSCs (cAT-MSCs) with a CBD-rich cannabis extract on cell morphology, viability, neurotrophic factor gene expression, and cytokine gene and protein expression. cAT-MSCs ( = 5) were primed for 24 h and divided into three groups: Control (C, unprimed), D1 (2.25 µM CBD), and D2 (225 nM CBD). No morphological or viability changes were observed. Gene expression analysis showed that groups D1 and D2 exhibited increased HGF expression. D1 also showed increased IDO and decreased BDNF expression. In contrast, no significant changes were observed in GDNF, IL-10, TNF-α, IFN-γ, or PTGES2. Regarding the cytokine profile, GM-CSF, IL-2, and IL-10 were undetectable. Notably, IL-8 and MCP-1 levels were significantly reduced in D1 compared to the control. These findings suggest that CBD priming modulates key regenerative and inflammatory mediators in cAT-MSCs, supporting its potential application in enhancing the efficacy of cell-based therapies. - Source: PubMed
Publication date: 2025/09/24
Perino Vinicius SkauFerreira Lucas Vinícius de OliveiraKamura Beatriz da CostaChimenes Natielly DiasOlbera Alisson Vinícius GimenesPereira Thiago TourinhoBraz Aline Márcia MarquesGolim Marjorie de AssisCarvalho Márcio deAmorim Rogério Martins - Genetic deletion or antibody blockade of platelet endothelial cell adhesion molecule-1 (PECAM; CD31) inhibits transendothelial migration (TEM) of leukocytes in all mouse strains studied except C57BL/6. A prior publication showed that this phenotype maps to a single 35.8-Mb locus on mouse chromosome 2, that contains the genes Ptgs1, Ptges, and Ptges2, which encode key enzymes involved in the prostaglandin E (PGE) synthesis pathway. PGE is a proinflammatory lipid mediator that binds four E prostanoid receptors (EPs 1 to 4). It was hypothesized that PGE signaling supports TEM via a CD31-independent mechanism. In vitro TEM assays demonstrate that PGE or 16,16-dimethyl PGE can restore transmigration of polymorphonuclear leukocytes and peripheral blood mononuclear cells despite a TEM blockade with anti-CD31. This protransmigratory effect could be blocked with the EP1 antagonist, SC-51089, or with transient receptor potential canonical 6 antagonist, BI-749327. 17-Phenyl trinor PGE, an agonist of EP1 and EP3, also restored transmigration of polymorphonuclear leukocytes blocked with anti-CD31. In vivo, PGE overcame an anti-CD31 blockade when administered to FVB/n mice in thioglycolate peritonitis or croton oil dermatitis models, whereas blocking EP1 with SC-51089 decreased TEM in C57BL/6 pecam1 mice. The findings support earlier data that identified PGE as a candidate inducer of CD31-independent TEM, and pinpoint EP1 as the receptor that relays that signal to activate transient receptor potential canonical 6. - Source: PubMed
Publication date: 2025/10/17
Hayashi VanessaSeidman Michael AMuller William A - Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple fluid-filled cysts in the kidneys, resulting in progressive decline and failure of renal function. Microsomal prostaglandin E synthase-2 (mPGES-2) is a unique bifunctional enzyme that catalyzes the conversion of prostaglandin H (PGH) to prostaglandin E (PGE) or to malondialdehyde (MDA) in conjunction with heme. PGE and MDA are key mediators that regulate cell growth and proliferation, respectively. In this study, we elucidated the functional role of mPGES-2 in ADPKD. By performing Western blot and immunohistochemical staining on the kidneys of patients with PKD and healthy controls, we showed that the expression levels of mPGES-2 markedly increased. We then crossed mPGES-2 knockout (Ptges2) mice with Ksp-Cre; pkd1 mice to generate mPGES-2 knockout ADPKD (Ptges2; PKD) mice. We showed that mPGES-2 depletion mitigated ADPKD progression in a mouse model. These findings were corroborated by in vitro experiments in embryonic kidney cells: the application of the mPGES-2 inhibitor SZ0232 (40, 80, and 160 μM) effectively suppressed cyst growth, suggesting a potential therapeutic option for ADPKD. Analysis of mPGES-2 metabolites revealed that mPGES-2 deficiency led to a reduction in PGE production, which has not been detected in other renal diseases, likely because of the diminished heme levels in ADPKD kidneys. Moreover, mPGES-2 was implicated in the regulation of the downstream signaling pathway involving β-catenin/STAT3-c-Myc via PGE-EP, which promoted abnormal proliferation of renal tubular epithelial cells and influenced cyst formation. Our findings suggest that targeting mPGES-2 is a viable therapeutic strategy for the management of ADPKD. - Source: PubMed
Publication date: 2025/10/17
Zhong Dan-DanHu ChengZhao Lan-LanShen YanZhang Ru-MengLiu YingLiu Bu-HuiSu WenYang Bao-XueXiong HuiGuo DongSun DongZou Ying-YingSun Ying - Bioconjugation chemistry has been a powerful avenue in expanding the repertoire of druggable proteome, as well as in identifying new E3 ligases to support targeted protein degradation (TPD). However, a large fraction of proteome remains inaccessible with existing covalent probes. Herein, we incorporated various electron-withdrawing groups into styrene derivatives and identified β-nitrostyrene as a cysteine-targeting reversible covalent warhead for target discovery. Through phenotypic screening and chemoproteomics platforms, we identified new ligandable sites such as C96 of SND1, C110 of PTGES2, modulating cell proliferation in an acute myeloid leukemia cell line. Moreover, incorporation of this warhead into the BRD4 inhibitor (+)-JQ1 demonstrated that the covalent handle engages the novel E3 ligase tripartite motif-containing 28 (TRIM28) at Cys232 residue, thereby promoting the targeted degradation. Notably, when transplanted into other protein-targeting ligands, the β-nitrostyrene warhead effectively induced protein degradation of EGFR, PDE5, BTK, LRRK2, and BCR-ABL/c-ABL without eliciting a hook effect. Importantly, the degraders demonstrate significantly enhanced antcancer effects compared to corresponding inhibitors. To our knowledge, this is the first report of small-molecular degraders engaging TRIM28 to support targeted protein degradation, and provides a rational pathway for design and development of potent monovalent degraders. - Source: PubMed
Publication date: 2025/06/29
Ouyang XinyaoChai XiaomengHuang LeiChen YubinLi ShengrongHuang WeizhenLi YifangDing KeLiu TongzhengTan YiLi Zhengqiu