Evidence map›Paper›PMID 29415757›Full record

ArticleArthritis research & therapy2018

Soluble uric acid increases PDZK1 and ABCG2 expression in human intestinal cell lines via the TLR4-NLRP3 inflammasome and PI3K/Akt signaling pathway.

Mo Chen, Xiaoyong Lu, Ci Lu, Ning Shen, Yujie Jiang, Menglu Chen, Huaxiang Wu

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 2 pooled it
6.5field-weighted citation impact, top 2% 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

57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 116 citations in OpenAlex.

  1. Pooled it
  2. Uremic Toxins in Organ Crosstalk.Frontiers in medicine · 2021
    Pooled it
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Association betweenFrontiers in medicine · 2025
    Article
  12. Review
  13. Review
  14. Article
  15. Frontiers in nutrition · 2024
    Article
  16. Review
  17. Article
  18. Biodegradation of Uric Acid byMicroorganisms · 2023
    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 2 institutions in 1 country.

Mo ChenDepartment of Rheumatology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Xiaoyong LuDepartment of Rheumatology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Ci LuDepartment of Rheumatology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Ning ShenDepartment of Rheumatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Yujie JiangDepartment of Rheumatology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Menglu ChenDepartment of Rheumatology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China.
Huaxiang WuDepartment of Rheumatology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, China. wuhx8855@zju.edu.cn.
Second Affiliated Hospital of Zhejiang University · CNZhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn addition to the kidney, the intestine is one of the most important organs involved in uric acid excretion. However, the mechanism of urate excretion in the intestine remains unclear. Therefore, the relationship between soluble uric acid and the gut excretion in human intestinal cells was explored. The relevant signaling molecules were then also examined.

methodsHT-29 and Caco-2 cell lines were stimulated with soluble uric acid. Western blotting and qRT-PCR were used to measure protein and mRNA levels. Subcellular fractionation methods and immunofluorescence were used to quantify the proteins in different subcellular compartments. Flow cytometry experiments examined the function of ATP-binding cassette transporter, subfamily G, member 2 (ABCG2). Small interfering RNA transfection was used to assess the interaction between ABCG2 and PDZ domain-containing 1 (PDZK1).

resultsSoluble uric acid increased the expression of PDZK1 and ABCG2. The stimulation of soluble uric acid also facilitated the translocation of ABCG2 from the intracellular compartment to the plasma membrane and increased its transport activity. Moreover, the upregulation of PDZK1 and ABCG2 by soluble uric acid was partially decreased by either TLR4-NLRP3 inflammasome inhibitors or PI3K/Akt signaling inhibitors. Furthermore, PDZK1 knockdown significantly inhibited the expression and transport activity of ABCG2 regardless of the activation by soluble uric acid, demonstrating a pivotal role for PDZK1 in the regulation of ABCG2.

conclusionsThese findings suggest that urate upregulates the expression of PDZK1 and ABCG2 for excretion in intestinal cells via activating the TLR4-NLRP3 inflammasome and PI3K/Akt signaling pathway.

Indexed as

ATP Binding Cassette Transporter, Subfamily G, Member 2Caco-2 CellsCarrier ProteinsColonGene ExpressionHT29 CellsHumansInflammasomesMembrane ProteinsNeoplasm ProteinsNLR Family, Pyrin Domain-Containing 3 ProteinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRNA InterferenceSignal TransductionSolubilityABCG2 protein, humanATP Binding Cassette Transporter, Subfamily G, Member 2Carrier ProteinsInflammasomesMembrane ProteinsNeoplasm ProteinsNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanPDZK1 protein, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTLR4 protein, humanToll-Like Receptor 4Uric AcidABCG2HyperuricemiaIntestinePDZK1

Identifiers

PMID29415757
PMCPMC5803867
OpenAlexW2801192639

What OpenQuestion holds

Textmetadata
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.