15-keto-Prostaglandin E2 exhibits bioactive role by modulating glomerular cytoarchitecture through EP2/EP4 receptors

Kourpa, Aikaterini; Kaiser-Graf, Debora; Sporbert, Anje; Philippe, Aurélie; Catar, Rusan; Rothe, Michael; Mangelsen, Eva; Schulz, Angela; Bolbrinker, Juliane; Kreutz, Reinhold; Panàkovà, Daniela

doi:10.1016/j.lfs.2022.121114

Cited by 3 publications

(3 citation statements)

References 82 publications

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“…For example, they have enabled living imaging of calcium signaling in developing podocytes [ 271 ], and made exciting observations of how blood flow regulates glomerular capillary formation [ 272 ]. Further, glomerular architecture in response to signaling has been examined, with new insights uncovered for the role of prostaglandin signaling [ 273 ]. Transgenics have also been leveraged so as to observe normal filtration with subsequent proximal tubule reabsorption and compare these events to cases of proteinuria and altered cargo processing [ 274 ].…”

Section: Discussionmentioning

confidence: 99%

Modeling Podocyte Ontogeny and Podocytopathies with the Zebrafish

Drummond

Ercanbrack

Wingert

2023

JDB

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Podocytes are exquisitely fashioned kidney cells that serve an essential role in the process of blood filtration. Congenital malformation or damage to podocytes has dire consequences and initiates a cascade of pathological changes leading to renal disease states known as podocytopathies. In addition, animal models have been integral to discovering the molecular pathways that direct the development of podocytes. In this review, we explore how researchers have used the zebrafish to illuminate new insights about the processes of podocyte ontogeny, model podocytopathies, and create opportunities to discover future therapies.

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Section: Discussionmentioning

confidence: 99%

Modeling Podocyte Ontogeny and Podocytopathies with the Zebrafish

Drummond

Ercanbrack

Wingert

2023

JDB

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“…A pathogenic role of signaling via the EP2 and possibly with lesser relevance via EP4 has been also suggested ( Penn et al, 2001 ). We recently demonstrated in a yeast model that PGE 2 and its downstream metabolite 15-keto-PGE 2 bind to both EP2 and EP4 in vitro ( Kourpa et al, 2022 ). Moreover, we showed in lipidomic analyses by LC/ESI-MS/MS that concerted EP2 and EP4 signaling mediates autocrine PGE 2 signaling in human podocytes ( Mangelsen et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a bioactive role of 15-keto-PGE 2 has been identified and its signaling through activation of the peroxisome proliferator activated receptor gamma (PPAR-γ) pathway investigated ( Chou et al, 2007 ; Lu et al, 2014 ; Chang et al, 2016 ; Chen et al, 2018 ). Effects of 15-keto-PGE 2 are mediated via EP2 and EP4 receptors in vitro and in vivo ( Endo et al, 2020 ; Kourpa et al, 2022 ). Previously, it has been shown that 15-keto-PGE 2 affects the glomerular morphology of zebrafish embryonic kidney ( Kourpa et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Tissue lipidomic profiling supports a mechanistic role of the prostaglandin E2 pathway for albuminuria development in glomerular hyperfiltration

Kaiser-Graf,

Schulz,

Mangelsen

et al. 2023

Front. Netw. Physiol.

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Background: Glomerular hyperfiltration (GH) is an important mechanism in the development of albuminuria in hypertension. The Munich Wistar Frömter (MWF) rat is a non-diabetic model of chronic kidney disease (CKD) with GH due to inherited low nephron number resulting in spontaneous albuminuria and podocyte injury. In MWF rats, we identified prostaglandin (PG) E2 (PGE2) signaling as a potential causative mechanism of albuminuria in GH.Method: For evaluation of the renal PGE2 metabolic pathway, time-course lipidomic analysis of PGE2 and its downstream metabolites 15-keto-PGE2 and 13-14-dihydro-15-keto-PGE2 was conducted in urine, plasma and kidney tissues of MWF rats and albuminuria-resistant spontaneously hypertensive rats (SHR) by liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS).Results: Lipidomic analysis revealed no dysregulation of plasma PGs over the time course of albuminuria development, while glomerular levels of PGE2 and 15-keto-PGE2 were significantly elevated in MWF compared to albuminuria-resistant SHR. Overall, averaged PGE2 levels in glomeruli were up to ×150 higher than the corresponding 15-keto-PGE2 levels. Glomerular metabolic ratios of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) were significantly lower, while metabolic ratios of prostaglandin reductases (PTGRs) were significantly higher in MWF rats with manifested albuminuria compared to SHR, respectively.Conclusion: Our data reveal glomerular dysregulation of the PGE2 metabolism in the development of albuminuria in GH, resulting at least partly from reduced PGE2 degradation. This study provides first insights into dynamic changes of the PGE2 pathway that support a role of glomerular PGE2 metabolism and signaling for early albuminuria manifestation in GH.

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Severity-Dependent Long-Term Post-Traumatic Changes in the Circulating Oxylipin Profile

Reinicke,

Zheng,

Rang

et al. 2024

IJMS

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Trauma causes the breakdown of membrane phospholipids and the subsequent degradation of the released polyunsaturated fatty acids (PUFAs) to partially bioactive oxylipins. Here, we screened for circulating PUFAs and oxylipins in patients (n = 34) differing from those of uninjured controls (n = 25) and analyzed their diagnostic potential. Patients were followed up for 1 to 240 h after minor/moderate, severe, and very severe injuries. Of the targeted oxylipins, 13 out of 80 (13/80) were detected in almost all patients and controls. Injury caused a long-term decrease in 9- and 13-hydroxyoctadecadienoic acids and in several dihydroxyeicosatetraenoic acids, the stable derivatives of bioactive anti-inflammatory epoxyeicosatrienoic acids, compared to controls. Frequently, these oxylipins correlated inversely to injury severity, days in the intensive care unit and hospital, and/or procalcitonin and pro-inflammatory cytokine levels 48 up to 240 h after trauma. Notably, 20/80 oxylipins were detected in some patients but not or less often in controls. Many of these oxylipins increased transiently immediately after injury. Their level is partly correlated with adverse clinical parameters at this early time point. The circulating oxylipidome was markedly affected by trauma. Several oxylipins showed injury-dependent alterations at different time points in the post-traumatic course.

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15-keto-Prostaglandin E2 exhibits bioactive role by modulating glomerular cytoarchitecture through EP2/EP4 receptors

Cited by 3 publications

References 82 publications

Modeling Podocyte Ontogeny and Podocytopathies with the Zebrafish

Modeling Podocyte Ontogeny and Podocytopathies with the Zebrafish

Tissue lipidomic profiling supports a mechanistic role of the prostaglandin E2 pathway for albuminuria development in glomerular hyperfiltration

Severity-Dependent Long-Term Post-Traumatic Changes in the Circulating Oxylipin Profile

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