Evidence map›Paper›PMID 25896349›Full record

ArticleJournal of lipid research2015

Regulation of autotaxin expression and secretion by lysophosphatidate and sphingosine 1-phosphate.

Matthew G K Benesch, Yuan Y Zhao, Jonathan M Curtis, Todd P W McMullen, David N Brindley

Open access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

75 citing papers in PubMed, 119 citations in OpenAlex.

  1. Trial
  2. Context-dependent lysophosphatidic acid signalling in inflammation: evidence hierarchy, myeloid regulation and translational gaps.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  3. Article
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  13. Review
  14. Lysophosphatidic acid receptor 1 inhibition: a potential treatment target for pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2024
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

15 more citing papers are in PubMed but not listed here.

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

5 authors at 1 institution in 1 country.

Matthew G K BeneschSignal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
Yuan Y ZhaoDepartments of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
Jonathan M CurtisDepartments of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
Todd P W McMullenSurgery, University of Alberta, Edmonton, Alberta, Canada.
David N BrindleySignal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
University of Alberta · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Autotaxin (ATX) is a secreted enzyme, which produces extracellular lysophosphatidate (LPA) from lysophosphatidylcholine (LPC). LPA activates six G protein-coupled receptors and this is essential for vasculogenesis during embryonic development. ATX is also involved in wound healing and inflammation, and in tumor growth, metastasis, and chemo-resistance. It is, therefore, important to understand how ATX is regulated. It was proposed that ATX activity is inhibited by its product LPA, or a related lipid called sphingosine 1-phosphate (S1P). We now show that this apparent inhibition is ineffective at the high concentrations of LPC that occur in vivo. Instead, feedback regulation by LPA and S1P is mediated by inhibition of ATX expression resulting from phosphatidylinositol-3-kinase activation. Inhibiting ATX activity in mice with ONO-8430506 severely decreased plasma LPA concentrations and increased ATX mRNA in adipose tissue, which is a major site of ATX production. Consequently, the amount of inhibitor-bound ATX protein in the plasma increased. We, therefore, demonstrate the concept that accumulation of LPA in the circulation decreases ATX production. However, this feedback regulation can be overcome by the inflammatory cytokines, TNF-α or interleukin 1β. This enables high LPA and ATX levels to coexist in inflammatory conditions. The results are discussed in terms of ATX regulation in wound healing and cancer.

Indexed as

Adipose TissueAnimalsCarbolinesGene Expression RegulationHumansInflammationLysophospholipase DLysophospholipidsMicePhosphoric Diester HydrolasesReceptors, G-Protein-CoupledSphingosineTumor Necrosis Factor-alphaWound HealingCarbolineslysophosphatidic acidLysophospholipase DLysophospholipidsONO-8430506Phosphoric Diester HydrolasesReceptors, G-Protein-CoupledSphingosinesphingosine 1-phosphateTNF protein, humanTumor Necrosis Factor-alphaautotaxin inhibitioncytokinesfluorescent substrate-3 assayinflammationlysophosphatidylcholine

Identifiers

PMID25896349
PMCPMC4442871
OpenAlexW1974170084

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.