Concerted EP2 and EP4 Receptor Signaling Stimulates Autocrine Prostaglandin E(2) Activation in Human Podocytes

Glomerular hyperfiltration is an important mechanism in the development of albuminuria. During hyperfiltration, podocytes are exposed to increased fluid flow shear stress (FFSS) in Bowman’s space. Elevated Prostaglandin E2 (PGE(2)) synthesis and upregulated cyclooxygenase 2 (Cox2) are associated wit...

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Autores principales: Mangelsen, Eva, Rothe, Michael, Schulz, Angela, Kourpa, Aikaterini, Panáková, Daniela, Kreutz, Reinhold, Bolbrinker, Juliane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290667/
https://www.ncbi.nlm.nih.gov/pubmed/32438662
http://dx.doi.org/10.3390/cells9051256
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author Mangelsen, Eva
Rothe, Michael
Schulz, Angela
Kourpa, Aikaterini
Panáková, Daniela
Kreutz, Reinhold
Bolbrinker, Juliane
author_facet Mangelsen, Eva
Rothe, Michael
Schulz, Angela
Kourpa, Aikaterini
Panáková, Daniela
Kreutz, Reinhold
Bolbrinker, Juliane
author_sort Mangelsen, Eva
collection PubMed
description Glomerular hyperfiltration is an important mechanism in the development of albuminuria. During hyperfiltration, podocytes are exposed to increased fluid flow shear stress (FFSS) in Bowman’s space. Elevated Prostaglandin E2 (PGE(2)) synthesis and upregulated cyclooxygenase 2 (Cox2) are associated with podocyte injury by FFSS. We aimed to elucidate a PGE(2) autocrine/paracrine pathway in human podocytes (hPC). We developed a modified liquid chromatography tandem mass spectrometry (LC/ESI-MS/MS) protocol to quantify cellular PGE(2), 15-keto-PGE(2), and 13,14-dihydro-15-keto-PGE(2) levels. hPC were treated with PGE(2) with or without separate or combined blockade of prostaglandin E receptors (EP), EP2, and EP4. Furthermore, the effect of FFSS on COX2, PTGER2, and PTGER4 expression in hPC was quantified. In hPC, stimulation with PGE(2) led to an EP2- and EP4-dependent increase in cyclic adenosine monophosphate (cAMP) and COX2, and induced cellular PGE(2). PTGER4 was downregulated after PGE(2) stimulation in hPC. In the corresponding LC/ESI-MS/MS in vivo analysis at the tissue level, increased PGE(2) and 15-keto-PGE(2) levels were observed in isolated glomeruli obtained from a well-established rat model with glomerular hyperfiltration, the Munich Wistar Frömter rat. COX2 and PTGER2 were upregulated by FFSS. Our data thus support an autocrine/paracrine COX2/PGE(2) pathway in hPC linked to concerted EP2 and EP4 signaling.
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spelling pubmed-72906672020-06-17 Concerted EP2 and EP4 Receptor Signaling Stimulates Autocrine Prostaglandin E(2) Activation in Human Podocytes Mangelsen, Eva Rothe, Michael Schulz, Angela Kourpa, Aikaterini Panáková, Daniela Kreutz, Reinhold Bolbrinker, Juliane Cells Article Glomerular hyperfiltration is an important mechanism in the development of albuminuria. During hyperfiltration, podocytes are exposed to increased fluid flow shear stress (FFSS) in Bowman’s space. Elevated Prostaglandin E2 (PGE(2)) synthesis and upregulated cyclooxygenase 2 (Cox2) are associated with podocyte injury by FFSS. We aimed to elucidate a PGE(2) autocrine/paracrine pathway in human podocytes (hPC). We developed a modified liquid chromatography tandem mass spectrometry (LC/ESI-MS/MS) protocol to quantify cellular PGE(2), 15-keto-PGE(2), and 13,14-dihydro-15-keto-PGE(2) levels. hPC were treated with PGE(2) with or without separate or combined blockade of prostaglandin E receptors (EP), EP2, and EP4. Furthermore, the effect of FFSS on COX2, PTGER2, and PTGER4 expression in hPC was quantified. In hPC, stimulation with PGE(2) led to an EP2- and EP4-dependent increase in cyclic adenosine monophosphate (cAMP) and COX2, and induced cellular PGE(2). PTGER4 was downregulated after PGE(2) stimulation in hPC. In the corresponding LC/ESI-MS/MS in vivo analysis at the tissue level, increased PGE(2) and 15-keto-PGE(2) levels were observed in isolated glomeruli obtained from a well-established rat model with glomerular hyperfiltration, the Munich Wistar Frömter rat. COX2 and PTGER2 were upregulated by FFSS. Our data thus support an autocrine/paracrine COX2/PGE(2) pathway in hPC linked to concerted EP2 and EP4 signaling. MDPI 2020-05-19 /pmc/articles/PMC7290667/ /pubmed/32438662 http://dx.doi.org/10.3390/cells9051256 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mangelsen, Eva
Rothe, Michael
Schulz, Angela
Kourpa, Aikaterini
Panáková, Daniela
Kreutz, Reinhold
Bolbrinker, Juliane
Concerted EP2 and EP4 Receptor Signaling Stimulates Autocrine Prostaglandin E(2) Activation in Human Podocytes
title Concerted EP2 and EP4 Receptor Signaling Stimulates Autocrine Prostaglandin E(2) Activation in Human Podocytes
title_full Concerted EP2 and EP4 Receptor Signaling Stimulates Autocrine Prostaglandin E(2) Activation in Human Podocytes
title_fullStr Concerted EP2 and EP4 Receptor Signaling Stimulates Autocrine Prostaglandin E(2) Activation in Human Podocytes
title_full_unstemmed Concerted EP2 and EP4 Receptor Signaling Stimulates Autocrine Prostaglandin E(2) Activation in Human Podocytes
title_short Concerted EP2 and EP4 Receptor Signaling Stimulates Autocrine Prostaglandin E(2) Activation in Human Podocytes
title_sort concerted ep2 and ep4 receptor signaling stimulates autocrine prostaglandin e(2) activation in human podocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290667/
https://www.ncbi.nlm.nih.gov/pubmed/32438662
http://dx.doi.org/10.3390/cells9051256
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