Enhancement of activated β1-integrin expression by prostaglandin E2 via EP receptors in isolated human coronary arterial endothelial cells: implication for the treatment of Kawasaki disease

Kajimoto, Madoka; Ichiyama, Takashi; Ueno, Yoshiko; Shiraishi, Masaya; Hasegawa, Motoharu; Furukawa, Susumu

doi:10.1007/s00011-008-8138-y

Cited by 13 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a key regulator of cellular signaling pathways that control cell proliferation and a protein downstream of PGE 2 , FAK is associated with proteins of the AA metabolic pathway. 11 , 14 , 32 – 34 For example, exogenous PGE 2 can increase FAK phosphorylation at Tyr397 in a concentration-dependent manner in HCC cells. At the same time, the selective COX-2 inhibitor celecoxib decreases FAK expression.…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy induces ovarian cancer cell repopulation through the caspase 3-mediated arachidonic acid metabolic pathway

Cui

Zhao

Pan

et al. 2017

OTT

View full text Add to dashboard Cite

Recurrence is one of the major causes of high mortality in ovarian cancer. However, the mechanism of ovarian cancer recurrence after chemotherapy has not been fully understood. In the present study, we investigated the effect of chemotherapy-induced tumor microenvironment on the proliferation of SKOV3 cells. We have shown that SKOV3 cells repopulated faster in the culture medium from apoptotic SKOV3 ovarian cancer cells after 24 h of etoposide phosphate (VP-16) treatment. We found that during apoptosis, cleaved caspase 3 could activate cytosolic calcium-independent phospholipase A2, which stimulated the release of arachidonic acid (AA) and triggered the production of prostaglandin E2 (PGE2). An increased level of phosphorylated focal adhesion kinase (FAK) subsequently facilitated the reproliferation of SKOV3 cells, and VP-16-induced repopulation effects were partially reversed by the FAK inhibitor PF562271. Furthermore, the plasma AA-to-PGE2 ratio and tumoral FAK expression of ovarian cancer patients after chemotherapy were significantly lower than those before chemotherapy. Taken together, our results indicate that chemotherapy-induced apoptotic cancer cells can produce PGE2-enriched microenvironment through caspase 3-mediated AA metabolic pathway, which could lead to the abnormal activation of FAK and eventually accelerate the repopulation of SKOV3 cells. Our study provides novel insight into a mechanism that may be utilized to prevent ovarian cancer recurrence in response to chemotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Chemotherapy induces ovarian cancer cell repopulation through the caspase 3-mediated arachidonic acid metabolic pathway

Cui

Zhao

Pan

et al. 2017

OTT

View full text Add to dashboard Cite

show abstract

“…β1-integrin was highly expressed in liver cancer tissue and mice model2029. PGE 2 improves β1-integrin expression in many cells30313233. However, the mechanism of PGE 2 -mediated β1-integrin expression remained unknown in HCC cells.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 stimulates β1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-κB pathway

Bai

Wang

Guo

et al. 2014

Sci Rep

View full text Add to dashboard Cite

Prostaglandin E2 (PGE2) has been implicated in cell invasion in hepatocellular carcinoma (HCC), via increased β1-integrin expression and cell migration; however, the mechanism remains unclear. PGE2 exerts its effects via four subtypes of the E prostanoid receptor (EP receptor 1–4). The present study investigated the effect of EP1 receptor activation on β1-integrin expression and cell migration in HCC. Cell migration increased by 60% in cells treated with 17-PT-PGE2 (EP1 agonist), which was suppressed by pretreatment with a β1-integrin polyclonal antibody. PGE2 increased β1-integrin expression by approximately 2-fold. EP1 receptor transfection or treatment with 17-PT-PGE2 mimicked the effect of PGE2 treatment. EP1 siRNA blocked PGE2-mediated β1-integrin expression. 17-PT-PGE2 treatment induced PKC and NF-κB activation; PKC and NF-κB inhibitors suppressed 17-PT-PGE2-mediated β1-integrin expression. FoxC2, a β1-integrin transcription factor, was also upregulated by 17-PT-PGE2. NF-κB inhibitor suppressed 17-PT-PGE2-mediated FoxC2 upregulation. Immunohistochemistry showed p65, FoxC2, EP1 receptor and β1-integrin were all highly expressed in the HCC cases. This study suggested that PGE2 upregulates β1-integrin expression and cell migration in HCC cells by activating the PKC/NF-κB signaling pathway. Targeting PGE2/EP1/PKC/NF-κB/FoxC2/β1-integrin pathway may represent a new therapeutic strategy for the prevention and treatment of this cancer.

show abstract

“…22) Another EP2 agonist, CP-533536, healed fractures when administered locally as a single dose in rat models of fracture healing. 23) Other compounds, 19 (R)-hydroxy PGE 2 24) and AH13205, also act as selective EP2 agonists which sprouted nerve fibers.…”

Section: Synthesized Ep Agonists I) Ep1 Agonistsmentioning

confidence: 99%

Roles of Prostaglandin E2 in Cardiovascular Diseases

et al. 2011

View full text Add to dashboard Cite

SummaryProstaglandin E2 (PGE 2 ) is produced in inflammatory responses and regulates a variety of immunological reactions through 4 different receptor subtypes; EP1, 2, 3 and 4. However, the precise role of each receptor in cardiovascular disease has not yet been elucidated. Enhanced expression of some EPs has been observed in clinical and experimental cardiovascular diseases. EP agonists have been developed to clarify the role of each receptor. Recently, we developed a novel selective agonist to examine the effects of EP4 on cardiac transplantation, myocardial ischemia, and myocarditis. Of note, a selective EP4 agonist attenuated inflammatory cytokines and chemokines via attenuation of macrophage activation in inflammatory heart diseases. In this review article, we discuss the effects of PGE 2 receptor agonists on the development of cardiovascular diseases. (Int Heart J 2011; 52: 266-269) Key words: Prostaglandin, Receptors, Chemokine, Macrophage, Heart P rostanoids are known to be multifunctional physiologic factors. They are produced by various stimuli and participate in local homeostasis and physiologic responses. They are synthesized from arachidonic acid and quickly released to the extracellular medium to send signals via prostanoid receptors.1) The prostanoid receptors, DP, EP, FP, IP and TP, are bound to PGD 2 , PGE 2 , PGF 2α , PGI 2 , and TXA 2 , respectively. 2)In the cardiovascular system, these receptors are expressed on various cells, such as cardiomyocytes, vascular endothelium and smooth muscle cells.3) They play an important role in modulating homeostasis in the development of cardiovascular diseases, such as thrombosis and atherosclerosis.4) Recent studies revealed that prostanoids play an important role in both the occurrence and suppression of various cardiovascular diseases, such as myocardial ischemia, cardiac hypertrophy, cardiac fibrosis, and atherosclerosis. 5) However, the detailed roles of prostanoids in cardiovascular disease have not yet been completely elucidated. To clarify the mechanisms, selective receptor agonists have been developed.Among the prostanoids, PGE 2 is known to play a key role in the pathogenesis of cardiovascular diseases. It was reported that a deficiency of PGE 2 synthase-1 reduced plaque burden in fat-diet low-density lipoprotein receptor knockout mice.6) Another report revealed that PGE 2 synthase-1 knockout mice showed impaired left ventricular contraction after acute myocardial infarction.7) These studies indicate that PGE 2 plays a pivotal role in cardiovascular inflammation. 8, 9) PGE 2 exerts their effects via G-protein-coupled receptors, and PGE 2 -mediated cardioprotection is involved in the EP receptor subtypes. 10)Each receptor has their unique signaling pathways. EP1 couples to Gq and increases intracellular Ca . EP3 couples to Gi and inhibits the increase of cAMP. EP2 and EP4 receptors are coupled to stimulate adenylate cyclase, which leads to the elevation of intracellular cAMP.11) In these EP receptors, EP3 and EP4 are known to have cardioprote...

show abstract

Enhancement of activated β1-integrin expression by prostaglandin E2 via EP receptors in isolated human coronary arterial endothelial cells: implication for the treatment of Kawasaki disease

Abstract: Our results suggest that PGE(2) mainly induces the activation of beta(1)-integrins via the EP(2) receptor in HCAEC. Our results further suggest that the EP(2) antagonist modulates the inflammatory response during KD vasculitis.

Cited by 13 publications

References 36 publications

Chemotherapy induces ovarian cancer cell repopulation through the caspase 3-mediated arachidonic acid metabolic pathway

Chemotherapy induces ovarian cancer cell repopulation through the caspase 3-mediated arachidonic acid metabolic pathway

Prostaglandin E2 stimulates β1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-κB pathway

Roles of Prostaglandin E2 in Cardiovascular Diseases

Contact Info

Product

Resources

About