Evidence map›Paper›PMID 22848392›Full record

ArticlePloS one2012

Downregulation of the NHE3-binding PDZ-adaptor protein PDZK1 expression during cytokine-induced inflammation in interleukin-10-deficient mice.

Henrike Lenzen, Maria Lünnemann, Andre Bleich, Michael P Manns, Ursula Seidler, Anne Jörns

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

24 citing papers in PubMed, 38 citations in OpenAlex.

  1. Milk andAmerican journal of physiology. Gastrointestinal and liver physiology · 2024
    Article
  2. Intestine-Specific NHE3 Deletion in Adulthood Causes Microbial Dysbiosis.Frontiers in cellular and infection microbiology · 2022
    Article
  3. Review
  4. Article
  5. Impairment of electroneutral NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2020
    Article
  6. Inhibition of intestinal villus cell Na/K-ATPase mediates altered glucose and NaCl absorption in obesity-associated diabetes and hypertension.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  7. (Patho-)Physiology of NaFrontiers in physiology · 2019
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Pathophysiology of Intestinal NaCellular and molecular gastroenterology and hepatology · 2017
    Article
  16. Article
  17. Article
  18. Article
  19. Review
  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

6 authors at 1 institution in 1 country.

Henrike LenzenDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. Lenzen.Henrike@mh-hannover.de
Maria Lünnemann
Andre Bleich
Michael P Manns
Ursula Seidler
Anne Jörns
Medizinische Hochschule Hannover · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImpaired salt and water absorption is an important feature in the pathogenesis of diarrhea in inflammatory bowel disease (IBD). We analyzed the expression of proinflammatory cytokines in the infiltrating immune cells and the function and expression of the Na(+)/H(+) exchanger isoform 3 (NHE3) and its regulatory PDZ-adaptor proteins NHERF1, NHERF2, and PDZK1 in the colon of interleukin-10-deficient (IL-10(-/-)) mice. METHODOLOGY/PRINCIPAL

findingsGene and protein expression were analyzed by real-time reverse transcription polymerase chain reaction (qRT-PCR), in situ RT-PCR, and immunohistochemistry. NHE3 activity was measured fluorometrically in apical enterocytes within isolated colonic crypts. Mice developed chronic colitis characterized by a typical immune cell infiltration composed of T-lymphocytes and macrophages, with high levels of gene and protein expression of the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α. In parallel, inducible nitric oxide synthase expression was increased while procaspase 3 expression was unaffected. Interferon-γ expression remained low. Although acid-activated NHE3 activity was significantly decreased, the inflammatory process did not affect its gene and protein expression or its abundance and localization in the apical membrane. However, expression of the PDZ-adaptor proteins NHERF2 and PDZK1 was downregulated. NHERF1 expression was unchanged. In a comparative analysis we observed the PDZK1 downregulation also in the DSS (dextran sulphate sodium) model of colitis. CONCLUSIONS/SIGNIFICANCE: The impairment of the absorptive function of the inflamed colon in the IL-10(-/-) mouse, in spite of unaltered NHE3 expression and localization, is accompanied by the downregulation of the NHE3-regulatory PDZ adaptors NHERF2 and PDZK1. We propose that the downregulation of PDZ-adaptor proteins may be an important factor leading to NHE3 dysfunction and diarrhea in the course of the cytokine-mediated inflammatory process in these animal models of IBD.

Indexed as

Down-RegulationInterleukin-10Intestinal AbsorptionAnimalsDextran SulfateDiarrheaDisease Models, AnimalInflammatory Bowel DiseasesInterleukin-1betaIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceMice, KnockoutPhosphoproteinsSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersDextran SulfateIL10 protein, mouseInterleukin-10Interleukin-1betaIntracellular Signaling Peptides and ProteinsMembrane ProteinsPDZK1 protein, mousePhosphoproteinsSlc9a3 protein, mouseSodium-Hydrogen Exchanger 3sodium-hydrogen exchanger regulatory factorSodium-Hydrogen ExchangersTumor Necrosis Factor-alpha

Identifiers

PMID22848392
PMCPMC3407152
OpenAlexW2027511620

What OpenQuestion holds

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LicenceCC BY
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.