Prostaglandin E2 activates Stat3 in neonatal rat ventricular cardiomyocytes: A role in cardiac hypertrophy

Frias, M; Rebsamen, Michela; Gerber-Wicht, Christine; Lang, Ursula

doi:10.1016/j.cardiores.2006.09.016

Cited by 67 publications

(63 citation statements)

References 39 publications

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“…Previous studies have shown that MEK and JNK pathways mainly induce Stat3 serine phosphorylation, which is required for transcriptional activities of Stat3 (36). Other studies also reported that Erk1/2 is indirectly involved in tyrosine Stat3 phosphorylation in cardiomyocytes (37,38). Interestingly, the current investigation observed many similarities, including delayed kinetics of Stat3 activation and involvement of de novo protein synthesis.…”

Section: Discussionsupporting

confidence: 60%

Transforming Growth Factor-β (TGF-β)-mediated Connective Tissue Growth Factor (CTGF) Expression in Hepatic Stellate Cells Requires Stat3 Signaling Activation

Liu

Meyer

et al. 2013

Journal of Biological Chemistry

163

135

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Section: Discussionsupporting

confidence: 60%

Transforming Growth Factor-β (TGF-β)-mediated Connective Tissue Growth Factor (CTGF) Expression in Hepatic Stellate Cells Requires Stat3 Signaling Activation

Liu

Meyer

et al. 2013

Journal of Biological Chemistry

163

135

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“…STAT3 can be activated by IL-6, IL-10 or VEGF; adenosine can mediate STAT3 activation via IL-10, as demonstrated in mouse macrophages, 38 while PGE 2 itself has also been shown to phosphorylate STAT3 in cardiomyocytes. 39 Signaling via STAT3 can upregulate CD73 in Th17 cells. 10 However, when STAT3 was blocked in our model, instead of inhibition of CD73 upregulation, we observed significantly enhanced CD73 expression.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E₂-mediated adenosinergic effects on CD14⁺cells: Self-amplifying immunosuppression in cancer

et al. 2017

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CD39 and CD73 are surface-expressed ectonucleotidases that hydrolyze ATP in a highly regulated, serial manner into ADP, AMP and adenosine. The end product, adenosine, has both tumor-promoting and immunosuppressive effects. The aim of this study was to determine CD73 expression on immune cells in pleural effusion (PE) in order to have a better understanding of the immune environment in mesothelioma. PE-or blood-derived CD14 C cells of mesothelioma patients and healthy donors were analyzed by flow cytometry for the expression of CD39 and CD73. CD73-induction was studied by exposure of CD14 C cells to the soluble fraction of PE (sPE), while the signaling mechanism, responsible for CD73 induction, by phosphoflow cytometry and receptor-inhibition studies. We observed CD73 expression on CD14 C cells in PE but not peripheral blood of mesothelioma patients or healthy donors. CD73 expression was inducible on CD14 C cells with sPE, cyclic-AMP (cAMP)-inducers (forskolin and prostaglandin-E 2 (PGE 2 )) and adenosine. Inhibition of PGE 2 receptors or adenosine A 2 receptors blocked CD73-induction by sPE. sPE treatment triggered protein kinase A and p38 activation. However, signal-transducer and activator of transcription 3 (STAT3)-blocking led to enhanced CD73 expression, demonstrating a hitherto unknown negative control of purinergic signaling by STAT3 in CD14 C cells. TNFa production by CD73 C CD14 C cells was significantly impaired in the presence of AMP, confirming immunosuppressive function. Taken together, CD73 expression can be induced by PGE 2 , cAMP or adenosine on human CD14 C cells. We suggest that targeting this autocrine loop is a valid therapeutic approach in mesothelioma that may also enhance immunotherapy.

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“…6 In addition, IL-6 and Stat-3 are involved in hypertrophy and protection from ischemic injury. 23 To investigate a potential mechanism underlying the effect of cardiac myocyte-specific EP 4 deletion on cardiac hypertrophy, we performed Western blot for phosphorylated Stat-3.…”

Section: Effect Of Ep 4 Deletion On Activation Of Stat-3mentioning

confidence: 99%

“…4 It also increased protein synthesis, cell size, and brain or B-type natriuretic peptide (BNP) expression in cardiac myocytes, all markers of hypertrophic growth. 5,6 We have also shown that myocardial infarction (MI) increased generation of PGE 2 accompanied by upregulation of COX-2 in the mouse heart, and treatment with a specific COX-2 inhibitor for 2 weeks improved cardiac function and reduced hypertrophy and fibrosis. 7 Given that COX-2 products have both deleterious and protective effects in the heart and vasculature, 8 -10 it is important to understand how PGE 2 affects the prohypertrophic response.…”

mentioning

confidence: 99%

Reduced Cardiac Remodeling and Function in Cardiac-Specific EP ₄ Receptor Knockout Mice With Myocardial Infarction

et al. 2008

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Abstract-We have shown previously that cyclooxygenase-2 inhibition reduces cardiac hypertrophy and fibrosis postmyocardial infarction (MI) in a mouse model and that prostaglandin E 2 stimulates cardiomyocyte hypertrophy in vitro through its EP 4 receptor. Because the role of cardiac myocyte EP 4 in cardiac function and hypertrophy in vivo is unknown, we generated mice lacking EP 4 only in cardiomyocytes (CM-EP 4 knockout [KO]). Twelve-to 14-week-old mice were evaluated using echocardiography and histology. There were no differences in ejection fraction, myocyte cross-sectional area, and interstitial collagen fraction between KO mice and littermate controls. To test the hypothesis that EP 4 is involved in cardiac remodeling after MI, we induced MI by ligating the left anterior descending coronary artery. Two weeks later, the mice were subjected to echocardiography, and hearts were removed for histology and Western blot. There was no difference in infarct size between KO mice and controls; however, KO mice showed less myocyte cross-sectional area and interstitial collagen fraction than controls. Also, CM-EP4 KO mice had reduced ejection fraction. Because the transcription factor Stat-3 is involved in hypertrophy and protection from ischemic injury, we tested whether it was activated in control and KO mouse hearts after MI. Western blot indicated that Stat-3 was activated in control hearts after MI but not in KO hearts. Thus, CM-EP4 deletion decreased hypertrophy, fibrosis, and activation of Stat-3. However, cardiac function was unexpectedly worsened in these mice. We conclude that cardiac myocyte EP 4 plays a role in hypertrophy via activation of Stat-3, a process that seems to be cardioprotective.

show abstract

Prostaglandin E2 activates Stat3 in neonatal rat ventricular cardiomyocytes: A role in cardiac hypertrophy

Abstract: In ventricular cardiomyocytes, PGE2 induces the activation of Stat3 which plays an essential role in PGE2-induced increase in cell size and protein synthesis. The activation of Stat3 occurs mainly through EP4 and involves ERK1/2 as well as newly synthesized protein(s).

Cited by 67 publications

References 39 publications

Transforming Growth Factor-β (TGF-β)-mediated Connective Tissue Growth Factor (CTGF) Expression in Hepatic Stellate Cells Requires Stat3 Signaling Activation

Transforming Growth Factor-β (TGF-β)-mediated Connective Tissue Growth Factor (CTGF) Expression in Hepatic Stellate Cells Requires Stat3 Signaling Activation

Prostaglandin E₂-mediated adenosinergic effects on CD14⁺cells: Self-amplifying immunosuppression in cancer

Reduced Cardiac Remodeling and Function in Cardiac-Specific EP ₄ Receptor Knockout Mice With Myocardial Infarction

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Prostaglandin E2 activates Stat3 in neonatal rat ventricular cardiomyocytes: A role in cardiac hypertrophy

Abstract: In ventricular cardiomyocytes, PGE2 induces the activation of Stat3 which plays an essential role in PGE2-induced increase in cell size and protein synthesis. The activation of Stat3 occurs mainly through EP4 and involves ERK1/2 as well as newly synthesized protein(s).

Cited by 67 publications

References 39 publications

Transforming Growth Factor-β (TGF-β)-mediated Connective Tissue Growth Factor (CTGF) Expression in Hepatic Stellate Cells Requires Stat3 Signaling Activation

Transforming Growth Factor-β (TGF-β)-mediated Connective Tissue Growth Factor (CTGF) Expression in Hepatic Stellate Cells Requires Stat3 Signaling Activation

Prostaglandin E2-mediated adenosinergic effects on CD14+cells: Self-amplifying immunosuppression in cancer

Reduced Cardiac Remodeling and Function in Cardiac-Specific EP 4 Receptor Knockout Mice With Myocardial Infarction

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Product

Resources

About

Prostaglandin E₂-mediated adenosinergic effects on CD14⁺cells: Self-amplifying immunosuppression in cancer

Reduced Cardiac Remodeling and Function in Cardiac-Specific EP ₄ Receptor Knockout Mice With Myocardial Infarction