Evidence map›Paper›PMID 28615031›Full record

ArticleArthritis research & therapy2017

Leucine-rich alpha 2 glycoprotein promotes Th17 differentiation and collagen-induced arthritis in mice through enhancement of TGF-β-Smad2 signaling in naïve helper T cells.

Hayato Urushima, Minoru Fujimoto, Takashi Mishima, Tomoharu Ohkawara, Hiromi Honda, Hyun Lee, Hirohisa Kawahata, Satoshi Serada, Tetsuji Naka

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.5field-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

34 citing papers in PubMed, 66 citations in OpenAlex.

  1. Article
  2. Do LRG1-SERPINA1 Interactions Modulate Fibrotic and Inflammatory Signatures in Rheumatoid Arthritis? A Proteomic and In Silico Investigation.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
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  20. LRG1: an emerging player in disease pathogenesis.Journal of biomedical science · 2022
    Review
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

9 authors at 2 institutions in 1 country.

Hayato UrushimaLaboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
Minoru FujimotoLaboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan. mfujimoto@nibiohn.go.jp.
Takashi MishimaLaboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
Tomoharu OhkawaraLaboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
Hiromi HondaLaboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
Hyun LeeLaboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
Hirohisa KawahataDepartment of Medical Technology, Morinomiya University of medical science, Osaka, Japan.
Satoshi SeradaLaboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
Tetsuji NakaLaboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
National Institute of Biomedical Innovation, Health and Nutrition · JPMorinomiya University of Medical Sciences · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLeucine-rich alpha 2 glycoprotein (LRG) has been identified as a serum protein elevated in patients with active rheumatoid arthritis (RA). Although the function of LRG is ill-defined, LRG binds with transforming growth factor (TGF)-β and enhances Smad2 phosphorylation. Considering that the imbalance between T helper 17 (Th17) cells and regulatory T cells (Treg) plays important roles in the pathogenesis of RA, LRG may affect arthritic pathology by enhancing the TGF-β-Smad2 pathway that is pivotal for both Treg and Th17 differentiation. The purpose of this study was to explore the contribution of LRG to the pathogenesis of arthritis, with a focus on the role of LRG in T cell differentiation.

methodsThe differentiation of CD4 T cells and the development of collagen-induced arthritis (CIA) were examined in wild-type mice and LRG knockout (KO) mice. To examine the influence of LRG on T cell differentiation, naïve CD4 T cells were isolated from LRG KO mice and cultured under Treg- or Th17-polarization condition in the absence or presence of recombinant LRG.

resultsIn the CIA model, LRG deficiency led to ameliorated arthritis and reduced Th17 differentiation with no influence on Treg differentiation. By addition of recombinant LRG, the expression of IL-6 receptor (IL-6R) was enhanced through TGF-β-Smad2 signaling. In LRG KO mice, the IL-6R expression and IL-6-STAT3 signaling was attenuated in naïve CD4 T cells, compared to wild-type mice.

conclusionsOur findings suggest that LRG upregulates IL-6R expression in naïve CD4 T cells by the enhancement of TGF-β-smad2 pathway and promote Th17 differentiation and arthritis development.

Indexed as

Signal TransductionAnimalsArthritis, ExperimentalCell DifferentiationGlycoproteinsMiceMice, Inbred C57BLMice, KnockoutReceptors, Interleukin-6Smad2 ProteinTh17 CellsT-Lymphocytes, Helper-InducerTransforming Growth Factor betaGlycoproteinsLRG1 protein, mouseReceptors, Interleukin-6Smad2 ProteinTransforming Growth Factor betaIL-6 receptorLeucine rich alpha2 glycoproteinSmad2TGF-βTh17

Identifiers

PMID28615031
PMCPMC5471956
OpenAlexW2624684659

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.