Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
YINGJI XIN
 + 1841 word(s) 1841 2021-07-09 11:05:35 |
2 Reference formatted
Ron Wang
 + 1 word(s) 1842 2021-08-02 08:31:28 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Xin, Y. Isookanin Inhibits PGE2-Mediated Angiogenesis. Encyclopedia. Available online: https://encyclopedia.pub/entry/12641 (accessed on 16 April 2024).
Xin Y. Isookanin Inhibits PGE2-Mediated Angiogenesis. Encyclopedia. Available at: https://encyclopedia.pub/entry/12641. Accessed April 16, 2024.
Xin, Yingji. "Isookanin Inhibits PGE2-Mediated Angiogenesis" Encyclopedia, https://encyclopedia.pub/entry/12641 (accessed April 16, 2024).
Xin, Y. (2021, August 02). Isookanin Inhibits PGE2-Mediated Angiogenesis. In Encyclopedia. https://encyclopedia.pub/entry/12641
Xin, Yingji. "Isookanin Inhibits PGE2-Mediated Angiogenesis." Encyclopedia. Web. 02 August, 2021.
Isookanin Inhibits PGE2-Mediated Angiogenesis
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms22126466

Inflammation is increasingly recognized as a critical mediator of angiogenesis, and unregulated angiogenic responses often involve human diseases. The importance of regulating angiogenesis in inflammatory diseases has been demonstrated through some successful cases of anti-angiogenesis therapies in related diseases, including arthritis, but it has been reported that some synthetic types of antiangiogenic drugs have potential side effects. In recent years, the importance of finding alternative strategies for regulating angiogenesis has begun to attract the attention of researchers. Therefore, identification of natural ingredients used to prevent or treat angiogenesis-related diseases will play a greater role. Isookanin is a phenolic flavonoid presented in Bidens extract, and it has been reported that isookanin possesses some biological properties, including antioxidative and anti-inflammatory effects, anti-diabetic properties, and an ability to inhibit α-amylase. However, its antiangiogenic effects and mechanism thereof have not been studied yet. In this study, our results indicate that isookanin has an effective inhibitory effect on the angiogenic properties of microvascular endothelial cells.

isookanin anti-angiogenesis HMEC-1 cell prostaglandin E2 (PGE2) cell cycle arrest ERK1/2 and CREB signaling pathway

1. Introduction

Angiogenesis is the formation of new capillaries from existing vasculature and is an integral biological process that occurs throughout life in a number of physiological and pathological processes [1]. It is known that angiogenesis is essential for reproduction, development, and wound repair, where it is highly regulated. However, many diseases are caused by unregulated angiogenesis, including cancer, rheumatoid arthritis, inflammatory bowel disease (IBD), and diabetic retinopathy [2][3]. In addition, angiogenesis is also involved in various skin diseases including psoriasis, telangiectasias, and rosacea, where various types of blood vessel growth can be observed in diseased skin [4].
Many potent proangiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiogenin, and transforming growth factor-β (TGF-β) have been found to be involved in angiogenesis [2]. Abnormal angiogenesis caused by these stimulants is accompanied by a series of endothelial cell behavioral changes associated with increased cell proliferation, cell migration and invasion, and the formation of new tubular structures [5]. Angiogenesis inhibitors targeting this set of mechanisms have been studied and applied in clinical trials, where the data have strongly suggested that suppressing aberrant angiogenesis may be a promising treatment for angiogenesis-related diseases [6][7].
Meanwhile, recent clinical and basic scientific studies indicate that angiogenic inducers involve (many) other factors, including inflammatory mediators [8]. Among the many inflammatory mediators, prostaglandins (PGs) are representative and are naturally occurring lipid compounds derived from the cyclooxygenase (COX)-mediated metabolism of arachidonic acid [9]. Prostaglandins link the interactions between various immune regulatory cells and are thought to play a key role in regulating the inflammatory response [10]. Prostaglandin E2 (PGE2) is the most abundant prostanoid in humans and the most important COX-2 mediated product found to date. PGE2 is involved in regulating many different fundamental biological functions, and its role in inflammation and immune response has been well established in previous studies [11][12].
To date, PGE2 has been the most researched inflammatory mediator in immune cells, and in recent years, a lot of attention has been paid to the other roles of PGE2 [13]. However, the mechanisms and effects of PGE2 on endothelial cells and angiogenesis have been less studied [14]. PGE2 affects target cells by binding four cognate receptors called EP1, EP2, EP3, and EP4, which belong to a large family of G protein-coupled receptors (GPCRs). Ligand binding of different EP receptors leads to different actions through activation of separate downstream signaling pathways [15]. Some prior studies have confirmed that PGE2 and EP receptors have a direct role in angiogenic gene expression and angiogenic cell behavior [14][16][17][18][19].
The importance of angiogenesis in inflammatory disease processes has been demonstrated by successful cases of antiangiogenic therapeutic trials for diseases such as asthma [20], rheumatic diseases [21], and dermatosis [22]. These treatments are commonly used FDA-approved drugs that target angiogenic factors or angiogenic factor signaling cascades [6]; however, these drugs are known to have some clinical limitations and some side effects associated with their administration [23][24].
Therefore, the importance of finding alternative strategies for controlling angiogenesis has begun to attract people’s attention, and the identification of natural compounds will play an important role in finding therapeutics for the prevention and treatment of angiogenesis-related diseases [25]. Isookanin (C15H12O6, molecular weight: 288.3) is a phenolic flavonoid presented in Bidens extract [26]. It has been reported that isookanin possesses some biological properties, including antioxidative [27][28] and anti-diabetic properties [27], anti-inflammatory effects [29] and an ability to inhibit α-amylase [26]. However, the antiangiogenic effects and mechanism thereof have not been studied yet.

2. Current Insights

Inflammatory mediators are well known for their role in inducing an appropriate immune response to external stimuli, and recently, they have also been shown to play an important role in the body’s response to vascular disease [30]. Previous studies have shown that the inflammatory response enhances angiogenesis and tumor growth [31]. Prostaglandins, especially PGE2, have been demonstrated to play an important role in immune regulation, and according to recent reports, PGE2 also plays a role in promoting the assembly of new blood vessels in angiogenesis [14]. The development of anti-angiogenesis agents has attracted great interest due to the high prevalence of angiogenesis-related diseases. The importance of antiangiogenic agents in the treatment of cancer is well established [32], and their role in the treatment of chronic inflammatory disorders is also gaining more support. In cases such as rheumatoid arthritis [33] and human IBD [34], it has been demonstrated that angiogenesis plays an important role in the pathophysiology of these chronic inflammatory diseases. There are several types of synthetic drugs for anti-angiogenesis therapy, but considering their side effects, it is worth investigating bioactive active compounds derived from natural products for the prevention and treatment of angiogenesis-related diseases [35]. Currently, a large variety of polyphenolic compounds from natural sources have drawn considerable attention for their multiplex biologic properties. Many natural compounds—for example, resveratrol, curcumin, or quercetin can target a wide variety of molecules, implying that natural products might be effective inhibitors [36]. Isookanin is a phenolic flavonoid component contained in some plants, such as Asteraceae [26] and Leguminosae [28], and its anti-inflammatory efficacy and mechanism of action have already been revealed in our previous research [29].
In this study, we investigated the role that isookanin plays in the process of PGE2-induced angiogenesis. The results of the LDH experiment show that isookanin has no cytotoxicity, and the results of MTT cell viability confirm that isookanin can reduce the proliferation of PGE2-induced HMEC-1 cells in a concentration-dependent manner, while not causing cell damage. In addition, we confirmed that isookanin inhibited the migration and tube formation of HMEC-1 cells induced by PGE2. These results support the potential of isookanin as an antiangiogenic agent. In addition, isookanin induces the S phase arrest of HMEC-1 cells through downregulating the expression of cell cycle-related proteins. Moreover, the flow cytometric data of cell cycle assay did not detect the increase of sub-G1 cells after isookanin treatment compared with the control group. This indicates that the antiangiogenic activity of isookanin is due to the inhibition of cell proliferation, not the induction of cell death.
PGE2 affects target cells by activating cognate receptors EP1-4 that belong to the G protein-coupled receptor superfamily of cell surface-expressed receptors [15]. The receptors demonstrate distinct, as well as opposing, effects on intracellular signaling events. The EP1 receptor couples to Gq and mediates a rise in intracellular calcium concentration, and the EP3 receptor couples to Gi, reducing cAMP concentration. Both EP2 and EP4 couple to Gs, leading to increased synthesis of cAMP and consequent activation of PKA [14]. Subsequent PKA activation is involved in multiple signaling, including activation of the cAMP response element (CREB) [37]. The transcription factor CREB plays a key role in controlling cell growth, survival, and cell cycle progression, and it plays an important role in the development of many cell types, including vascular smooth muscle cells [38], adipocytes [39], glioma cell [40], and vascular endothelial cells [41]. Multiple intracellular signaling kinases can induce the phosphorylation of CREB, including extracellular signal regulated kinases (ERKs) [40][42]. Moreover, the ERK signaling cascade is a central MAPK pathway that plays a role in the regulation of various cellular processes, such as proliferation, differentiation, survival, and apoptosis under some conditions [43]. For example, Pozzi et al. [44] demonstrated an EP4-mediated PI3K/ERK signaling pathway in mouse colon carcinoma cells. Activation of the ERK1/2 pathway is required for the growth, proliferation, and migration of endothelial cells, and this pathway is considered an important target for antiangiogenic agents [45][46].
In recent studies, it is known that PGE2 can promote cell growth by activating multiple signaling pathways involved in cell proliferation and that both MAPK and cAMP/PKA pathways are required for PGE2-induced cell proliferation [40][47]. In this study, PGE2 was shown to increase phosphorylation of ERK1/2 and CREB; therefore, PGE2-induced proliferation is associated with activation of ERK1/2 and CREB in vascular endothelial cells. In addition, isookanin exhibits the efficacy of inhibiting phosphorylation of both ERK 1/2 and CREB induced by PGE2. These results suggest that the mechanism by which isookanin inhibits the proliferation of vascular endothelial cells is by inhibition of ERK1/2 and CREB phosphorylation. However, these results should be confirmed by further experiments to determine whether isookanin inhibits CREB activation through ERK1/2 dependence or acts directly on CREB.
PGE2 may induce angiogenesis by acting indirectly on a variety of cell types to produce proangiogenic factors. Indeed, PGE2 stimulation of airway smooth muscle, endometrium, or colon cancer cells leads to increased production of VEGF, bFGF, or CXCL1 that, in turn, act on target endothelial cells to promote the angiogenesis [48][49][50]. In addition, previous studies have reported that PGE2 acts directly on endothelial cells, promoting the creation of new blood vessels through activation of G protein-coupled receptor EP4 and its downstream pathway [14]. Of all the PGE2 receptors, the roles of the EP4 receptor in health and disease have received much attention [51]. Chell et al. [52] reported that EP4 receptor protein expression was increased in colorectal cancers, as well as in adenomas when compared with normal colonic epithelium. EP receptor overexpression—and thus upregulation of various signaling cascades associated with angiogenic tumorigenesis, PGE2 modification of the tumor microenvironment, and evasion of the immune system—is regulated through the EP receptors [53]. Therefore, the direct effect of isookanin on the expression of the EP receptor was confirmed and is presented in Supplementary Materials. The result shows that isookanin effectively inhibited the expression of EP4 (Figure S1 in Supplementary Materials). These results suggest that isookanin possibly regulates downstream signaling by inhibiting the expression of EP4, and thereby inhibiting angiogenesis. However, to confirm the effect between the suppression of EP4 expression and downstream signaling, additional experiments are required. In addition, recent studies have reported that several specific receptors may be involved in the angiogenesis of PGE2. Finetti et al. [54] reported that PGE2 primes the angiogenic switch through a synergistic interaction with the fibroblast growth factor-2 pathway. There is also a report claiming that EP2 receptor agonists stimulate angiogenesis to promote adipogenesis [55]. Based on these studies, it can be expected that several specific receptors, including EP4, are the major receptors responsible for PGE2-induced angiogenesis. To identify the role of specific receptors for PGE2 in an angiogenesis model, further studies using specific EP antagonists or gene silencing are required.

References

  1. Adair, T.H.; Montani, J.-P. Angiogenesis, Colloquium Series on Integrated Systems Physiology: From Molecule to Function; Morgan & Claypool Life Sciences: San Rafael, CA, USA, 2010; pp. 1–84.
  2. Folkman, J.; Shing, Y. Angiogenesis. J. Biol. Chem. 1992, 267, 10931–10934.
  3. Carmeliet, P. Angiogenesis in health and disease. Nat. Med. 2003, 9, 653–660.
  4. Velasco, P.; Lange-Asschenfeldt, B. Dermatological aspects of angiogenesis. Br. J. Dermatol. 2002, 147, 841–852.
  5. van Hinsbergh, V.W.; Collen, A.; Koolwijk, P. Angiogenesis and anti-angiogenesis: Perspectives for the treatment of solid tumors. Ann. Oncol. 1999, 10, S60–S63.
  6. Carmeliet, P.; Jain, R.K. Molecular mechanisms and clinical applications of angiogenesis. Nature 2011, 473, 298–307.
  7. Kerbel, R.; Folkman, J. Clinical translation of angiogenesis inhibitors. Nat. Rev. Cancer 2002, 2, 727–739.
  8. Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674.
  9. Korbecki, J.; Baranowska-Bosiacka, I.; Gutowska, I.; Chlubek, D. Cyclooxygenase pathways. Acta Biochim. Pol. 2014, 61.
  10. Ricciotti, E.; FitzGerald, G.A. Prostaglandins and inflammation. Atertio. Thromb. Vasc. Biol. 2011, 31, 986–1000.
  11. Dey, I.; Lejeune, M.; Chadee, K. Prostaglandin E2 receptor distribution and function in the gastrointestinal tract. Br. J. Pharmacol. 2006, 149, 611–623.
  12. Park, J.Y.; Pillinger, M.H.; Abramson, S.B. Prostaglandin E2 synthesis and secretion: The role of PGE2 synthases. Clin. Immunol. 2006, 119, 229–240.
  13. Legler, D.F.; Bruckner, M.; Uetz-von Allmen, E.; Krause, P. Prostaglandin E2 at new glance: Novel insights in functional diversity offer therapeutic chances. Int. J. Biochem. Cell Biol. 2010, 42, 198–201.
  14. Zhang, Y.; Daaka, Y. PGE2 promotes angiogenesis through EP4 and PKA Cγ pathway. Blood J. Am. Soc. Hematol. 2011, 118, 5355–5364.
  15. Sugimoto, Y.; Narumiya, S. Prostaglandin E receptors. J. Biol. Chem. 2007, 282, 11613–11617.
  16. Hatazawa, R.; Tanigami, M.; Izumi, N.; Kamei, K.; Tanaka, A.; Takeuchi, K. Prostaglandin E 2 stimulates VEGF expression in primary rat gastric fibroblasts through EP4 receptors. Inflammopharmacology 2007, 15, 214–217.
  17. Rao, R.; Redha, R.; Macias-Perez, I.; Su, Y.; Hao, C.; Zent, R.; Breyer, M.D.; Pozzi, A. Prostaglandin E2-EP4 receptor promotes endothelial cell migration via ERK activation and angiogenesis in vivo. J. Biol. Chem. 2007, 282, 16959–16968.
  18. Muller, M.; Sales, K.J.; Katz, A.A.; Jabbour, H.N. Seminal plasma promotes the expression of tumorigenic and angiogenic genes in cervical adenocarcinoma cells via the E-series prostanoid 4 receptor. Endocrinology 2006, 147, 3356–3365.
  19. Yanni, S.E.; Barnett, J.M.; Clark, M.L.; Penn, J.S. The role of PGE2 receptor EP4 in pathologic ocular angiogenesis. Investig. Ophthalmol. Vis. Sci. 2009, 50, 5479–5486.
  20. Olivieri, D.; Chetta, A. Therapeutic perspectives in vascular remodeling in asthma and chronic obstructive pulmonary disease. Angiogenesis Lymphangiogenesis Clin. Implic. 2014, 99, 216–225.
  21. Zhang, W.; Li, F.; Gao, W. Tripterygium wilfordii inhibiting angiogenesis for rheumatoid arthritis treatment. J. Natl. Med. Assoc. 2017, 109, 142–148.
  22. Arbiser, J.L.; Govindarajan, B.; Battle, T.E.; Lynch, R.; Frank, D.A.; Ushio-Fukai, M.; Perry, B.N.; Stern, D.F.; Bowden, G.T.; Liu, A. Carbazole is a naturally occurring inhibitor of angiogenesis and inflammation isolated from antipsoriatic coal tar. J. Investig. Dermatol. 2006, 126, 1396–1402.
  23. Chen, H.X.; Cleck, J.N. Adverse effects of anticancer agents that target the VEGF pathway. Nat. Rev. Clin. Oncol. 2009, 6, 465.
  24. Des Guetz, G.; Uzzan, B.; Chouahnia, K.; Morère, J.-F. Cardiovascular toxicity of anti-angiogenic drugs. Target. Oncol. 2011, 6, 197–202.
  25. Rajasekar, J.; Perumal, M.K.; Vallikannan, B. A critical review on anti-angiogenic property of phytochemicals. J. Nutr. Biochem. 2019, 71, 1–15.
  26. Yang, X.-W.; Huang, M.-Z.; Jin, Y.-S.; Sun, L.-N.; Song, Y.; Chen, H.-S. Phenolics from Bidens bipinnata and their amylase inhibitory properties. Fitoterapia 2012, 83, 1169–1175.
  27. Ahmed, D.; Kumar, V.; Sharma, M.; Verma, A. Target guided isolation, in-vitro antidiabetic, antioxidant activity and molecular docking studies of some flavonoids from Albizzia Lebbeck Benth. bark. BMC Complement. Altern. Med. 2014, 14, 155.
  28. Wang, W.; Chen, W.; Yang, Y.; Liu, T.; Yang, H.; Xin, Z. New phenolic compounds from Coreopsis tinctoria Nutt. and their antioxidant and angiotensin I-converting enzyme inhibitory activities. J. Agric. Food Chem. 2015, 63, 200–207.
  29. Xin, Y.-J.; Choi, S.; Roh, K.-B.; Cho, E.; Ji, H.; Weon, J.B.; Park, D.; Whang, W.K.; Jung, E. Anti-Inflammatory Activity and Mechanism of Isookanin, Isolated by Bioassay-Guided Fractionation from Bidens pilosa L. Molecules 2021, 26, 255.
  30. Szekanecz, Z.; Koch, A.E. Mechanisms of disease: Angiogenesis in inflammatory diseases. Nat. Clin. Pract. Rheumatol. 2007, 3, 635–643.
  31. Kofler, S.; Nickel, T.; Weis, M. Role of cytokines in cardiovascular diseases: A focus on endothelial responses to inflammation. Clin. Sci. 2005, 108, 205–213.
  32. Rajabi, M.; Mousa, S.A. The role of angiogenesis in cancer treatment. Biomedicines 2017, 5, 34.
  33. Szekanecz, Z.; Gáspár, L.; Koch, A.E. Angiogenesis in rheumatoid arthritis. Front Biosci 2005, 10, 1739–1740.
  34. Pousa, I.; Maté, J.; Gisbert, J. Angiogenesis in inflammatory bowel disease. Eur. J. Clin. Investig. 2008, 38, 73–81.
  35. EL-Meghawry, E.; Rahman, H.; Abdelkarim, G.; Najda, A. Natural products against cancer angiogenesis. Tumor Biol. 2016, 37, 14513–14536.
  36. Ji, H.F.; Li, X.J.; Zhang, H.Y. Natural products and drug discovery: Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia? EMBO Rep. 2009, 10, 194–200.
  37. New, D.C.; Wong, Y.H. Molecular mechanisms mediating the G protein-coupled receptor regulation of cell cycle progression. J. Mol. Signal. 2007, 2, 1–15.
  38. Klemm, D.J.; Watson, P.A.; Frid, M.G.; Dempsey, E.C.; Schaack, J.; Colton, L.A.; Nesterova, A.; Stenmark, K.R.; Reusch, J.E.-B. cAMP response element-binding protein content is a molecular determinant of smooth muscle cell proliferation and migration. J. Biol. Chem. 2001, 276, 46132–46141.
  39. Reusch, J.E.; Colton, L.A.; Klemm, D.J. CREB activation induces adipogenesis in 3T3-L1 cells. Mol. Cell. Biol. 2000, 20, 1008–1020.
  40. Daniel, P.; Filiz, G.; Brown, D.; Hollande, F.; Gonzales, M.; D’Abaco, G.; Papalexis, N.; Phillips, W.; Malaterre, J.; Ramsay, R.G. Selective CREB-dependent cyclin expression mediated by the PI3K and MAPK pathways supports glioma cell proliferation. Oncogenesis 2014, 3, e108.
  41. Mayo, L.D.; Kessler, K.M.; Pincheira, R.; Warren, R.S.; Donner, D.B. Vascular endothelial cell growth factor activates CRE-binding protein by signaling through the KDR receptor tyrosine kinase. J. Biol. Chem. 2001, 276, 25184–25189.
  42. Zhang, C.-J.; Liu, C.; Wang, Y.-X.; Zhu, N.; Hu, Z.-Y.; Liao, D.-F.; Qin, L. Long non-coding RNA-SRA promotes neointimal hyperplasia and vascular smooth muscle cells proliferation via MEK-ERK-CREB pathway. Vascul. Pharmacol. 2019, 116, 16–23.
  43. Shaul, Y.D.; Seger, R. The MEK/ERK cascade: From signaling specificity to diverse functions. Biochim. Biophys. Acta BBA Mol. Cell Res. 2007, 1773, 1213–1226.
  44. Pozzi, A.; Yan, X.; Macias-Perez, I.; Wei, S.; Hata, A.N.; Breyer, R.M.; Morrow, J.D.; Capdevila, J.H. Colon carcinoma cell growth is associated with prostaglandin E2/EP4 receptor-evoked ERK activation. J. Biol. Chem. 2004, 279, 29797–29804.
  45. Kim, G.D. Hesperetin inhibits vascular formation by suppressing of the PI3K/AKT, ERK, and p38 MAPK signaling pathways. Prev. Nutr. Food Sci. 2014, 19, 299.
  46. Song, Y.; Dai, F.; Zhai, D.; Dong, Y.; Zhang, J.; Lu, B.; Luo, J.; Liu, M.; Yi, Z. Usnic acid inhibits breast tumor angiogenesis and growth by suppressing VEGFR2-mediated AKT and ERK1/2 signaling pathways. Angiogenesis 2012, 15, 421–432.
  47. Ansari, K.M.; Rundhaug, J.E.; Fischer, S.M. Multiple Signaling Pathways Are Responsible for Prostaglandin E2–Induced Murine Keratinocyte Proliferation. Mol. Cancer Res. 2008, 6, 1003–1016.
  48. Bradbury, D.; Clarke, D.; Seedhouse, C.; Corbett, L.; Stocks, J.; Knox, A. Vascular endothelial growth factor induction by prostaglandin E2 in human airway smooth muscle cells is mediated by E prostanoid EP2/EP4 receptors and SP-1 transcription factor binding sites. J. Biol. Chem. 2005, 280, 29993–30000.
  49. Battersby, S.; Sales, K.; Williams, A.; Anderson, R.; Gardner, S.; Jabbour, H. Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway. Hum. Reprod. 2007, 22, 36–44.
  50. Wang, D.; Wang, H.; Brown, J.; Daikoku, T.; Ning, W.; Shi, Q.; Richmond, A.; Strieter, R.; Dey, S.K.; DuBois, R.N. CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer. J. Exp. Med. 2006, 203, 941–951.
  51. Konya, V.; Marsche, G.; Schuligoi, R.; Heinemann, A. E-type prostanoid receptor 4 (EP4) in disease and therapy. Pharmacol. Ther. 2013, 138, 485–502.
  52. Chell, S.D.; Witherden, I.R.; Dobson, R.R.; Moorghen, M.; Herman, A.A.; Qualtrough, D.; Williams, A.C.; Paraskeva, C. Increased EP4 receptor expression in colorectal cancer progression promotes cell growth and anchorage independence. Cancer Res. 2006, 66, 3106–3113.
  53. Musser, M.L.; Viall, A.K.; Phillips, R.L.; Hostetter, J.M.; Johannes, C.M. Gene expression of prostaglandin EP4 receptor in three canine carcinomas. BMC Vet. Res. 2020, 16, 1–10.
  54. Finetti, F.; Donnini, S.; Giachetti, A.; Morbidelli, L.; Ziche, M. Prostaglandin E2 primes the angiogenic switch via a synergic interaction with the fibroblast growth factor-2 pathway. Circ. Res. 2009, 105, 657–666.
  55. Tsuji, T.; Yamaguchi, K.; Kikuchi, R.; Itoh, M.; Nakamura, H.; Nagai, A.; Aoshiba, K. Promotion of adipogenesis by an EP2 receptor agonist via stimulation of angiogenesis in pulmonary emphysema. Prostaglandins Other Lipid Mediat. 2014, 112, 9–15.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Biology
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
YINGJI XIN
View Times: 365
Revisions: 2 times (View History)
Update Date: 02 Aug 2021
Table of Contents
    1000/1000
    Hot Most Recent
    Feedback