Evidence map›Paper›PMID 26995650›Full record

ArticleDiabetologia2016

PGE2 receptor EP3 inhibits water reabsorption and contributes to polyuria and kidney injury in a streptozotocin-induced mouse model of diabetes.

Ramzi Hassouneh, Rania Nasrallah, Joe Zimpelmann, Alex Gutsol, David Eckert, Jamie Ghossein, Kevin D Burns, Richard L Hébert

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 39 citations in OpenAlex.

  1. Novel Roles of GPCRs in the Renal Collecting Duct.Physiology (Bethesda, Md.) · 2026
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  8. The Link between Prostanoids and Cardiovascular Diseases.International journal of molecular sciences · 2023
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  16. Arachidonic Acid Metabolism and Kidney Inflammation.International journal of molecular sciences · 2019
    Review
  17. Article
  18. Article
  19. Mammalian urine concentration: a review of renal medullary architecture and membrane transporters.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2018
    Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Ramzi HassounehDepartment of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Room 2514, Ottawa, ON, Canada, K1H 8M5.
Rania NasrallahDepartment of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Room 2514, Ottawa, ON, Canada, K1H 8M5.
Joe ZimpelmannOttawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
Alex GutsolOttawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
David EckertDepartment of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Room 2514, Ottawa, ON, Canada, K1H 8M5.
Jamie GhosseinDepartment of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Room 2514, Ottawa, ON, Canada, K1H 8M5.
Kevin D BurnsDepartment of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Room 2514, Ottawa, ON, Canada, K1H 8M5.
Richard L HébertDepartment of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Room 2514, Ottawa, ON, Canada, K1H 8M5. rlhebert@uottawa.ca.
University of Ottawa · CAOttawa Hospital · CA

Funding

CIHR 220694
6 · The paper itself

Abstract

aims/hypothesisThe first clinical manifestation of diabetes is polyuria. The prostaglandin E2 (PGE2) receptor EP3 antagonises arginine vasopressin (AVP)-mediated water reabsorption and its expression is increased in the diabetic kidney. The purpose of this work was to study the contribution of EP3 to diabetic polyuria and renal injury.

methodsMale Ep 3 (-/-) (also known as Ptger3 (-/-)) mice were treated with streptozotocin (STZ) to generate a mouse model of diabetes and renal function was evaluated after 12 weeks. Isolated collecting ducts (CDs) were microperfused to study the contribution of EP3 to AVP-mediated fluid reabsorption.

resultsEp 3 (-/-)-STZ mice exhibited attenuated polyuria and increased urine osmolality compared with wild-type STZ (WT-STZ) mice, suggesting enhanced water reabsorption. Compared with WT-STZ mice, Ep 3 (-/-)-STZ mice also had increased protein expression of aquaporin-1, aquaporin-2, and urea transporter A1, and reduced urinary AVP excretion, but increased medullary V2 receptors. In vitro microperfusion studies indicated that Ep 3 (-/-) and WT-STZ CDs responded to AVP stimulation similarly to those of wild-type mice, with a 60% increase in fluid reabsorption. In WT non-injected and WT-STZ mice, EP3 activation with sulprostone (PGE2 analogue) abrogated AVP-mediated water reabsorption; this effect was absent in mice lacking EP3. A major finding of this work is that Ep 3 (-/-)-STZ mice showed blunted renal cyclooxygenase-2 protein expression, reduced renal hypertrophy, reduced hyperfiltration and reduced albuminuria, as well as diminished tubular dilation and nuclear cysts. CONCLUSIONS/

interpretationTaken together, the data suggest that EP3 contributes to diabetic polyuria by inhibiting expression of aquaporins and that it promotes renal injury during diabetes. EP3 may prove to be a promising target for more selective management of diabetic kidney disease.

Indexed as

AnimalsAquaporinsArginine VasopressinDisease Models, AnimalKidneyMaleMicePolyuriaReceptors, Prostaglandin EReceptors, Prostaglandin E, EP3 SubtypeStreptozocinWaterAquaporinsArginine VasopressinPtger3 protein, mouseReceptors, Prostaglandin EReceptors, Prostaglandin E, EP3 SubtypeStreptozocinWaterAquaporinsArginine vasopressinDiabetic kidney diseaseIsolated perfused cortical collecting ductPGE2/EP3 receptorsPolyuriaUrine concentrating function

Identifiers

PMID26995650
OpenAlexW2298127727

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.