Evidence map›Paper›PMID 25505251›Full record

ArticleThe Journal of biological chemistry2015

A gut microbial metabolite of linoleic acid, 10-hydroxy-cis-12-octadecenoic acid, ameliorates intestinal epithelial barrier impairment partially via GPR40-MEK-ERK pathway.

Junki Miyamoto, Taichi Mizukure, Si-Bum Park, Shigenobu Kishino, Ikuo Kimura, Kanako Hirano, Paolo Bergamo, Mauro Rossi, Takuya Suzuki, Makoto Arita and 2 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

121 citing papers in PubMed, 255 citations in OpenAlex.

  1. Article
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  17. Veterinary sciences · 2025
    Article
  18. Review
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61 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

12 authors at 6 institutions in 2 countries.

Junki MiyamotoFrom the Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8528, Japan.
Taichi MizukureFrom the Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8528, Japan.
Si-Bum Parkthe Graduate School of Agriculture, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan.
Shigenobu Kishinothe Graduate School of Agriculture, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan.
Ikuo Kimurathe Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachicho, Sakyo-ku, Kyoto 606-8501, Japan, the Graduate School of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
Kanako Hiranothe Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachicho, Sakyo-ku, Kyoto 606-8501, Japan.
Paolo Bergamothe Institute of Food Sciences, National Research Council, via Roma 64, Avellino 83100, Italy, and.
Mauro Rossithe Institute of Food Sciences, National Research Council, via Roma 64, Avellino 83100, Italy, and.
Takuya SuzukiFrom the Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8528, Japan.
Makoto Aritathe Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Jun Ogawathe Graduate School of Agriculture, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan, ogawa@kais.kyoto-u.ac.jp.
Soichi TanabeFrom the Graduate School of Biosphere Science, Hiroshima University, 1-4-4 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8528, Japan, stanabe@hiroshima-u.ac.jp.
Hiroshima University · JPKyoto University · JPInstitute of Food Science · ITNational Research Council · ITRIKEN Center for Integrative Medical Sciences · JPTokyo University of Agriculture and Technology · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gut microbial metabolites of polyunsaturated fatty acids have attracted much attention because of their various physiological properties. Dysfunction of tight junction (TJ) in the intestine contributes to the pathogenesis of many disorders such as inflammatory bowel disease. We evaluated the effects of five novel gut microbial metabolites on tumor necrosis factor (TNF)-α-induced barrier impairment in Caco-2 cells and dextran sulfate sodium-induced colitis in mice. 10-Hydroxy-cis-12-octadecenoic acid (HYA), a gut microbial metabolite of linoleic acid, suppressed TNF-α and dextran sulfate sodium-induced changes in the expression of TJ-related molecules, occludin, zonula occludens-1, and myosin light chain kinase. HYA also suppressed the expression of TNF receptor 2 (TNFR2) mRNA and protein expression in Caco-2 cells and colonic tissue. In addition, HYA suppressed the protein expression of TNFR2 in murine intestinal epithelial cells. Furthermore, HYA significantly up-regulated G protein-coupled receptor (GPR) 40 expression in Caco-2 cells. It also induced [Ca(2+)]i responses in HEK293 cells expressing human GPR40 with higher sensitivity than linoleic acid, its metabolic precursor. The barrier-recovering effects of HYA were abrogated by a GPR40 antagonist and MEK inhibitor in Caco-2 cells. Conversely, 10-hydroxyoctadacanoic acid, which is a gut microbial metabolite of oleic acid and lacks a carbon-carbon double bond at Δ12 position, did not show these TJ-restoring activities and down-regulated GPR40 expression. Therefore, HYA modulates TNFR2 expression, at least partially, via the GPR40-MEK-ERK pathway and may be useful in the treatment of TJ-related disorders such as inflammatory bowel disease.

Indexed as

AnimalsCaco-2 CellsColitisEpithelial CellsFemaleFlow CytometryHumansImmunohistochemistryIntestinesLinoleic AcidMAP Kinase Signaling SystemMiceMice, Inbred BALB COleic AcidsReceptors, G-Protein-Coupled10-hydroxy-12-octadecenoic acidFFAR1 protein, humanFfar1 protein, mouseLinoleic AcidOleic AcidsReceptors, G-Protein-CoupledCaco-2ColitisEpithelial CellG Protein-coupled ReceptorLinoleic AcidMetaboliteMicrobiomeTight JunctionTumor Necrosis Factor (TNF)

Identifiers

PMID25505251
PMCPMC4317025
OpenAlexW2055291719

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.