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Search results for: EP4

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#35037469   2022/01/17 To Up

Intact prostaglandin signaling through EP2 and EP4 receptors in stromal progenitor cells is required for normal development of the renal cortex in mice.

Cyclooxygenase (Cox) inhibitors are known to have severe side effects during renal development. These consist of reduced renal function, underdeveloped subcapsular glomeruli, interstitial fibrosis and thinner cortical tissue. Global genetic deletion of Cox-2 mimics the phenotype observed after application of Cox-inhibitors. This study aimed to investigate which cell-types express Cox-2 and the prostaglandin E receptors and what functions are mediated through this pathway during renal development. Expression of EP2 and EP4 mRNA was detected by RNAscope mainly in descendants of FoxD1 stromal progenitors, EP1 and EP3 on the other hand were expressed in tubules. Cox-2 mRNA was detected in medullary interstitial cells and macula densa cells. Functional investigations were performed with a cell specific approach to delete Cox-2, EP2 and EP4 in FoxD1 stromal progenitor cells. Our data show that the Cox-2 expression in macula densa cells is sufficient to drive renal development. Deletion of EP2 or EP4 in FoxD1 cells had no functional effect on renal development. Codeletion of EP2 and EP4 in FoxD1 stromal cells, however, led to severe glomerular defects and strong decline of GFR (1316±69,7 in controls vs. 644,1±64,58 µl/min/100gBW in FoxD1 EP2 EP4 mice), similar to the global deletion of Cox-2. Furthermore EP2/EP4 deficient mice showed a significant increase in collagen production with a strong downregulation of renal renin expression. This study shows the distinct localization of EP receptors in mice. Functionally we could identify EP2 and EP4 receptors in stromal FoxD1 progenitor cells as essential receptor subtypes for normal renal development.
Michaela Alexandra Anna Fuchs, Julia Schrankl, Christina Leupold, Charlotte Wagner, Armin Kurtz, Katharina Broeker

1146 related Products with: Intact prostaglandin signaling through EP2 and EP4 receptors in stromal progenitor cells is required for normal development of the renal cortex in mice.

0.1ml (1mg/ml) 100 G300 units1.00 flask

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#35020527   2022/01/12 To Up

Receptor-mediated activation of CFTR via prostaglandin signaling pathways in the airway.

Cystic fibrosis (CF) is a genetic disease caused by mutations of the gene encoding a cAMP-activated Cl channel, the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR modulator therapies consist of small-molecule drugs that rescue mutant CFTR. Regimens of single or combinations of CFTR modulators still rely on endogenous levels of cAMP to regulate CFTR activity. We investigated CFTR activation by the natural mediator prostaglandin E2 (PGE2) and lubiprostone and tested the hypothesis that receptor-mediated CFTR activators can be used in combination with currently available CFTR modulators to increase function of mutant CFTR. Primary cultured airway epithelia were assayed in Ussing chambers. Experimental CFTR activators and established CFTR modulators were applied for 24 h and/or acutely and analyzed for their effect on CFTR activity as measured by changes in short-circuit current (I). In non-CF airway epithelia, acute application of lubiprostone and PGE2 activated CFTR to levels comparable to forskolin. Pre-treatment (24 h) with antagonists to prostaglandin receptors EP2 and EP4 abolished the ability of lubiprostone to acutely activate CFTR. In F508del homozygous airway epithelia pre-treated with the triple combination of elexacaftor, tezacaftor, and ivacaftor (ELEXA/TEZ/IVA; i.e., Trikafta), acute application of lubiprostone was able to maximally activate CFTR. Prolonged (24 h) co-treatment of F508del homozygous epithelia with ELEXA/TEZ/IVA and lubiprostone increased acute CFTR activation by ~60% compared to treatment with ELEXA/TEZ/IVA alone. This work establishes the feasibility of targeting prostaglandin receptors to activate CFTR on the airway epithelia and demonstrates that co-treatment with lubiprostone can further restore modulator-rescued CFTR.
Ciaran A Shaughnessy, Sangya Yadav, Preston E Bratcher, Pamela L Zeitlin

1891 related Products with: Receptor-mediated activation of CFTR via prostaglandin signaling pathways in the airway.

2 Pieces/Box2 Pieces/Box100 μg100ug2 Pieces/Box100ug Lyophilized7 inhibitors100ug100 μg100ug Lyophilized100ug

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#35013936   2022/01/10 To Up

COX-2/PGE2 Pathway Inhibits the Ferroptosis Induced by Cerebral Ischemia Reperfusion.

Cerebral ischemia reperfusion (I/R) injury easily develops in ischemic stroke, resulting in more serious injury. Ferroptosis is involved in cerebral I/R injury, but the mechanism remains unclear. Prostaglandin E2 (PGE2) is potential to regulate ferroptosis. This study mainly explored the regulation effects of PGE2 on ferroptosis induced by cerebral I/R. We first detected PGE2 levels and ferroptosis status in 11 human brain tissues. Then, we induced a cerebral I/R animal model to examine ferroptosis status in cerebral I/R. We further injected a ferroptosis inhibitor to define the response of the PGE2 pathway to ferroptosis. Finally, we injected PGE2 and pranoprofen to explore the regulation of the cyclooxygenases 2 (COX-2)/PGE2 pathway on ferroptosis in cerebral I/R. We found that PGE2 release was correlated with the levels of reactive oxygen species, malondialdehyde, glutathione peroxidase 4, COX-2, and Spermidine/spermine N1-acetyltransferase 1. Ferroptosis can be induced by cerebral I/R, while inhibition of ferroptosis induced by cerebral I/R can inactivate PGE2 synthases, degrade enzyme, and parts of PGE2 receptors, and reduce cerebral infarct volume. In turn, PGE2 inhibited ferroptosis through the reduction of Fe, glutathione oxidation, and lipid peroxidation, while pranoprofen, one of the COX inhibitors, played an opposite role. In conclusion, PGE2 was positively correlated with ferroptosis, inhibition of ferroptosis induced by cerebral I/R can inactivate COX-2/PGE2 pathway, and PGE2 inhibited ferroptosis induced by cerebral I/R, possibly via PGE2 receptor 3 and PGE2 receptor 4. Graphical abstract Inhibition of ferroptosis inactivates the COX-2/PGE2 pathway. Cerebral ischemia reperfusion injury induces the secretion of PGE2. After the inhibition of ferroptosis by Fer-1, the expression of cyclooxygenases (COX-1 and COX-2) decreased, and PGE2 synthases cPGES, mPGES-1, and mPGES-2 were also reduced. At the same time, the PGE2 degradation enzyme 15-PGDH was also reduced. Changes in these enzymes ultimately result in the declination of PGE2. Besides, the expression of PGE2 receptors EP3 and EP4 is also inhibited, indicating that the function they mediate is also impaired. In conclusion, after cerebral ischemia reperfusion injury, the inhibition of ferroptosis inactivates the COX-2/PGE2 pathway.
Yunfei Xu, Ying Liu, Kexin Li, Dun Yuan, Shun Yang, Lin Zhou, Yao Zhao, Shuying Miao, Caihong Lv, Jie Zhao

2672 related Products with: COX-2/PGE2 Pathway Inhibits the Ferroptosis Induced by Cerebral Ischemia Reperfusion.

1.5x10(6) cells12 Pieces/Box200 units96T50 ul100 1 ml2 Pieces/Box12 Pieces/Box

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#35003129   2021/12/22 To Up

Marek's Disease Virus Modulates T Cell Proliferation Activation of Cyclooxygenase 2-Dependent Prostaglandin E2.

Marek's disease virus (MDV), an avian alphaherpesvirus, infects chickens, transforms CD4+ T cells, and induces immunosuppression early during infection. However, the exact mechanisms involved in MDV-induced immunosuppression are yet to be identified. Here, our results demonstrate that MDV infection and induces activation of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). This exerts its inhibitory effects on T cell proliferation at day 21 post infection PGE2 receptor 2 (EP2) and receptor 4 (EP4). Impairment of the MDV-induced T cell proliferation was associated with downregulation of IL-2 and transferrin uptake in a COX-2/PGE2 dependent manner . Interestingly, oral administration of a COX-2 inhibitor, meloxicam, during MDV infection inhibited COX-2 activation and rescued T cell proliferation at day 21 post infection. Taken together, our results reveal a novel mechanism that contributes to immunosuppression in the MDV-infected chickens.
Nitin Kamble, Angila Gurung, Benedikt B Kaufer, Ansar Ahmed Pathan, Shahriar Behboudi

2901 related Products with: Marek's Disease Virus Modulates T Cell Proliferation Activation of Cyclooxygenase 2-Dependent Prostaglandin E2.

2500 Tests0.5 mg96 tests

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#34938150   2021/12/02 To Up

Changing prostaglandin E2 (PGE) signaling during lesional progression and exacerbation of endometriosis by inhibition of PGE receptor EP2 and EP4.

We investigated the change, if any, in prostaglandin E2 (PGE) signaling in endometriotic lesions of different developmental stages in mouse. In addition, we evaluated the effect of treatment of mice with induced deep endometriosis (DE) with inhibitors of PGE receptor subtypes EP2 and EP4 and metformin.
Qingqing Huang, Xishi Liu, Sun-Wei Guo

2501 related Products with: Changing prostaglandin E2 (PGE) signaling during lesional progression and exacerbation of endometriosis by inhibition of PGE receptor EP2 and EP4.

50 ug 100ug200ul50 ug 100ug0.1 mg100ug100.00 ul200 100ug

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#34938147   2021/11/01 To Up

Higher fibrotic content of endometriotic lesions is associated with diminished prostaglandin E2 signaling.

While the prevailing view holds that the prostaglandin E2 (PGE) signaling plays a vital role in endometriosis, PGE also is known to be anti-fibrotic. We investigated the immunostaining of COX-2, EP2, and EP4, along with fibrotic content in ovarian endometrioma (OE) and deep endometriosis (DE) lesions, and in OE lesions from adolescent and adult patients. In addition, we evaluated the effect of substrate stiffness on the expression of COX-2, EP2, and EP4 in endometrial stromal cells.
Qingqing Huang, Xishi Liu, Sun-Wei Guo

2055 related Products with: Higher fibrotic content of endometriotic lesions is associated with diminished prostaglandin E2 signaling.

0.1 ml 100ug Lyophilized100ug Lyophilized100ug Lyophilized100 ul100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized

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#34927727   2021/12/20 To Up

Prostaglandin signaling in ciliogenesis and development.

Prostaglandin (PG) signaling regulates a wide variety of physiological and pathological processes, including body temperature, cardiovascular homeostasis, reproduction, and inflammation. Recent studies have revealed that PGs play pivotal roles in embryo development, ciliogenesis, and organ formation. Prostaglandin E2 (PGE2) and its receptor EP4 modulate ciliogenesis by increasing the anterograde intraflagellar transport. Many G-protein-coupled receptors (GPCRs) including EP4 are localized in cilia for modulating cAMP signaling under various conditions. During development, PGE2 signaling regulates embryogenesis, hepatocyte differentiation, hematopoiesis, and kidney formation. Prostaglandins are also essential for skeletal muscle repair. This review outlines recent advances in understanding the functions and mechanisms of prostaglandin signaling in ciliogenesis, embryo development, and organ formation.
Daqing Jin, Tao P Zhong

2745 related Products with: Prostaglandin signaling in ciliogenesis and development.

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#34885255   2021/12/06 To Up

Basosquamous Carcinoma: A Commentary.

Basosquamous carcinoma is a rare, aggressive non-melanoma skin cancer with features that lie between those of basal cell carcinoma and squamous cell carcinoma. A lot of controversy has been raised around the classification, pathogenesis, histologic morphology, biologic behavior, prognosis and management of this tumor. This is a narrative review based on an electronic search of articles published in PubMed in English language which had in their title the terms "basosquamous carcinoma" and/or "metatypical carcinoma of the skin". The aim of this review was to summarize and evaluate current data regarding epidemiology, clinical presentation, dermoscopic and histopathologic characteristics, as well as the genetics and management of BSC, in order to shed some more light onto this intriguing entity. As a conclusion, dermoscopy, deep incisional biopsies and immunohistologic techniques (Ber-EP4) should be applied in clinically suspicious lesions in order to achieve an early diagnosis and better prognosis of this tumor. Surgical treatments, including wide excision and Mohs' micrographic surgery, remain the treatment of choice. Finally, vismodegib, a Hedgehog pathway inhibitor, must be thoroughly investigated, with large controlled trials, since it may offer an alternative solution to irresectable or difficult-to-treat, locally advanced cases of basosquamous carcinoma.
Christina Fotiadou, Zoe Apalla, Elizabeth Lazaridou

1211 related Products with: Basosquamous Carcinoma: A Commentary.



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#34877506   2021/11/15 To Up

Logical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes.

Psoriasis is a chronic skin disease, in which immune cells and keratinocytes keep each other in a state of inflammation. It is believed that phospholipase A (PLA)-dependent eicosanoid release plays a key role in this. T-helper (Th) 1-derived cytokines are established activators of phospholipases in keratinocytes, whereas Th17-derived cytokines have largely unknown effects. Logical model simulations describing the function of cytokine and eicosanoid signaling networks combined with experimental data suggest that Th17 cytokines stimulate proinflammatory cytokine expression in psoriatic keratinocytes via activation of cPLAα-Prostaglandin E-EP4 signaling, which could be suppressed using the anti-psoriatic calcipotriol. cPLAα inhibition and calcipotriol distinctly regulate expression of key psoriatic genes, possibly offering therapeutic advantage when applied together. Model simulations additionally suggest EP4 and protein kinase cAMP-activated catalytic subunit alpha as drug targets that may restore a normal phenotype. Our work illustrates how the study of complex diseases can benefit from an integrated systems approach.
Eirini Tsirvouli, Felicity Ashcroft, Berit Johansen, Martin Kuiper

2204 related Products with: Logical and experimental modeling of cytokine and eicosanoid signaling in psoriatic keratinocytes.

500 mg16 Arrays/Slide25 mg50 ug 10 mg4 Arrays/Slide100ug10 ug4 Membranes/Box4 Membranes/Box25 mg 5 G

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#34829941   2021/11/18 To Up

Dose-Dependent Effects of a Novel Selective EP Prostaglandin Receptor Agonist on Treatment of Critical Size Femoral Bone Defects in a Rat Model.

Difficulties in treating pseudarthrosis and critical bone defects are still evident in physicians' clinical routines. Bone morphogenetic protein 2 (BMP-2) has shown promising osteoinductive results but also considerable side effects, not unexpected given that it is a morphogen. Thus, the bone regenerative potential of the novel selective, non-morphogenic EP prostaglandin receptor agonist KMN-159 was investigated in this study. Therefore, mineralized collagen type-1 matrices were loaded with different amounts of BMP-2 or KMN-159 and implanted into a 5 mm critical-sized femoral defect in rats. After 12 weeks of observation, micro-computed tomography scans were performed to analyze the newly formed bone volume (BV) and bone mineral density (BMD). Histological analysis was performed to evaluate the degree of defect healing and the number of vessels, osteoclasts, and osteoblasts. Data were evaluated using Kruskal-Wallis followed by Dunn's post hoc test. As expected, animals treated with BMP-2, the positive control for this model, showed a high amount of newly formed BV as well as bone healing. For KMN-159, a dose-dependent effect on bone regeneration could be observed up to a dose optimum, demonstrating that this non-morphogenic mechanism of action can stimulate bone formation in this model system.
Corina Vater, Elisabeth Mehnert, Henriette Bretschneider, Julia Bolte, Lisa Findeisen, Lucas-Maximilian Matuszewski, Stefan Zwingenberger

2261 related Products with: Dose-Dependent Effects of a Novel Selective EP Prostaglandin Receptor Agonist on Treatment of Critical Size Femoral Bone Defects in a Rat Model.

100 UG100 μg100ug Lyophilized100ug100 μg96 assays 100ug Lyophilized100ug Lyophilized100ug

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