Evidence map›Paper›PMID 24700876›Full record

ArticleJournal of the American Society of Nephrology : JASN2014

Phosphodiesterase 1A modulates cystogenesis in zebrafish.

Caroline R Sussman, Christopher J Ward, Amanda C Leightner, Jordan L Smith, Reema Agarwal, Peter C Harris, Vicente E Torres

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
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  10. Pro: Tolvaptan delays the progression of autosomal dominant polycystic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019
    Article
  11. Article
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  14. The regulatory 1α subunit of protein kinase A modulates renal cystogenesis.American journal of physiology. Renal physiology · 2017
    Article
  15. Article
  16. Review
  17. Article
  18. Modulation of Polycystic Kidney Disease Severity by Phosphodiesterase 1 and 3 Subfamilies.Journal of the American Society of Nephrology : JASN · 2016
    Article
  19. Article
  20. Article
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

7 authors at 1 institution in 1 country.

Caroline R SussmanNephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota sussman.carli@mayo.edu.
Christopher J WardNephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota.
Amanda C LeightnerNephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota.
Jordan L SmithNephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota.
Reema AgarwalNephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota.
Peter C HarrisNephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota.
Vicente E TorresNephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota.
Mayo Clinic · US

Funding

Pilot and FeasibilityP30DK090728 · NIDDK · MAYO CLINIC ROCHESTER · PI ROMERO, MICHAEL F. · 2010 to 2019
$11.8M
Transgenic and Knockout Models of ADPKDR01DK059597 · NIDDK · MAYO CLINIC ROCHESTER · PI Peter C. Harris · 2002 to 2026
$9.5M
RENIN ANGIOTENSIN SYSTEM IN THE PATHOGENESIS OF ADPKDR01DK044863 · NIDDK · MAYO CLINIC ROCHESTER · PI TORRES, VICENTE E · 1991 to 2019
$4.5M
Novel treatment for polycystic kidney diseaseR56DK044863 · NIDDK · MAYO CLINIC ROCHESTER · PI TORRES, VICENTE E · 2015 to 2015
$119k
NIDDK NIH HHS DK059597NIDDK NIH HHS DK090728NIDDK NIH HHS DK44863NIDDK NIH HHS P30 DK090728NIDDK NIH HHS R01 DK044863NIDDK NIH HHS R01 DK059597NIDDK NIH HHS R56 DK044863
6 · The paper itself

Abstract

Substantial evidence indicates the importance of elevated cAMP in polycystic kidney disease (PKD). Accumulation of cAMP in cystic tissues may be, in part, caused by enhanced adenylyl cyclase activity, but inhibition of cAMP degradation by phosphodiesterases (PDE) likely has an important role, because cAMP is inactivated much faster than it is synthesized. PDE1 is the only PDE family activated by Ca(2+), which is reduced in PKD cells. To assess the contribution of the PDE1A subfamily to renal cyst formation, we examined the expression and function of PDE1A in zebrafish. We identified two splice isoforms with alternative starts corresponding to human PDE1A1 and PDE1A4. Expression of the two isoforms varied in embryos and adult tissues, and both isoforms hydrolyzed cAMP with Ca(2+)/calmodulin dependence. Depletion of PDE1A in zebrafish embryos using splice- and translation-blocking morpholinos (MOs) caused pronephric cysts, hydrocephalus, and body curvature. Human PDE1A RNA and the PKA inhibitors, H89 and Rp-cAMPS, partially rescued phenotypes of pde1a morphants. Additionally, MO depletion of PDE1A aggravated phenotypes in pkd2 morphants, causing more severe body curvature, and human PDE1A RNA partially rescued pkd2 morphant phenotypes, pronephric cysts, hydrocephalus, and body curvature. Together, these data indicate the integral role of PDE1A and cAMP signaling in renal development and cystogenesis, imply that PDE1A activity is altered downstream of polycystin-2, and suggest that PDE1A is a viable drug target for PKD.

Indexed as

Amino Acid SequenceAnimalsCyclic AMPCyclic Nucleotide Phosphodiesterases, Type 1Disease Models, AnimalEmbryo, NonmammalianHumansHydrocephalusKidneyMolecular Sequence DataPhenotypePolycystic Kidney DiseasesTRPP Cation ChannelsZebrafishCyclic AMPCyclic Nucleotide Phosphodiesterases, Type 1TRPP Cation Channels

Identifiers

PMID24700876
PMCPMC4178429
OpenAlexW2171536458

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.