Evidence map›Paper›PMID 28875549›Full record

ArticleInternational journal of cancer2018

The contribution of toll-like receptor signaling to the development of liver fibrosis and cancer in hepatocyte-specific TAK1-deleted mice.

Isabelle Jingyi Song, Yoon Mee Yang, Sayaka Inokuchi-Shimizu, Yoon Seok Roh, Ling Yang, Ekihiro Seki

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

35 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Review
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  9. Review
  10. In Vivo and In Vitro Models to Study Liver Fibrosis: Mechanisms and Limitations.Cellular and molecular gastroenterology and hepatology · 2023
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Smad3 Phospho-Isoform Signaling in Nonalcoholic Steatohepatitis.International journal of molecular sciences · 2022
    Review
  16. Comparison of gut microbiota in male MAFLD patients with varying liver stiffness.Frontiers in cellular and infection microbiology · 2022
    Article
  17. Article
  18. Review
  19. Article
  20. Pattern recognition receptors in health and diseases.Signal transduction and targeted therapy · 2021
    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

6 authors at 2 institutions in 3 countries.

Isabelle Jingyi SongDivision of Gastroenterology, Department of Medicine, University of California San Diego, School of Medicine, La Jolla, California, 92093, USA.
Yoon Mee YangDivision of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA.
Sayaka Inokuchi-ShimizuDivision of Gastroenterology, Department of Medicine, University of California San Diego, School of Medicine, La Jolla, California, 92093, USA.
Yoon Seok RohDivision of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA.
Ling YangDivision of Gastroenterology, Department of Medicine, University of California San Diego, School of Medicine, La Jolla, California, 92093, USA.
Ekihiro SekiDivision of Gastroenterology, Department of Medicine, University of California San Diego, School of Medicine, La Jolla, California, 92093, USA.ORCID 0000-0002-9472-6085
Cedars-Sinai Medical Center · USUniversity of California San Diego · US

Funding

Yeast Genetics and Stress Response Genes-BiomedicalP42ES010337 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2000 to 2022
$69.8M
LPS binding to TLR4 regulates hepatic stellate cell activation and fibrosisR01DK085252 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EKIHIRO SEKI · 2011 to 2026
$4.8M
Synergistic Actions By Multiple Toll-Like Receptors in Alcoholic Liver DiseaseR01AA020172 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SEKI, EKIHIRO · 2010 to 2014
$1.8M
Multidisciplinary Pulmonary Research Training ProgramT32HL134637 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI NOBLE, PAUL WESLEY · 2017 to 2021
$1.3M
Alcohol enhances colon cancer liver metastasis via cancer-associated fibroblastsR21AA025841 · NIAAA · CEDARS-SINAI MEDICAL CENTER · PI SEKI, EKIHIRO · 2017 to 2018
$459k
NHLBI NIH HHS T32 HL134637NIAAA NIH HHS R01 AA020172NIAAA NIH HHS R21 AA025841NIDDK NIH HHS R01 DK085252NIEHS NIH HHS P42 ES010337
6 · The paper itself

Abstract

Hepatocyte death is associated with liver inflammation, fibrosis and hepatocellular carcinoma (HCC). Damaged cells trigger inflammation through activation of Toll-like receptors (TLRs). Although the role of TLR4 in HCC development has been reported, the role of TLR9 in the development of HCC remains elusive. To investigate the role of TLR4 and TLR9 signaling in liver inflammation-fibrosis-cancer axis, we took advantage of mice with hepatic deletion of transforming growth factor-β-activated kinase 1 (Tak1ΔHep) that develop spontaneous liver injury, inflammation, fibrosis, and HCC, recapitulating the pathology of human HCC. We generated double knockout mice lacking genes of our interest with hepatic Tak1. Tak1ΔHep mice and Tlr4-deficient Tak1ΔHep mice had similar serum ALT levels, but Tlr4-deficient Tak1ΔHep mice exhibited significantly reduced macrophage infiltration, myofibroblast activation and tumor formation. Ablation of TLR9 reduced spontaneous liver injury, inflammation, fibrosis, and cancer development in Tak1ΔHep mice. In addition, the common adaptor, myeloid differentiation factor 88 (MyD88)-deficient Tak1ΔHep mice also attenuated liver injury, macrophage recruitment, collagen deposition, and tumor growth compared with control Tak1ΔHep mice. Genetic ablation of TNF receptor type I (TNFR) in Tak1ΔHep mice remarkably reduced liver inflammation-fibrosis-cancer axis. Surprisingly, disruption of interleukin-1 receptor (IL-1R) had no effect on liver injury and tumor formation, although Il1r-deficient Tak1ΔHep showed attenuated macrophage infiltration and collagen deposition. In conclusion, TLR4- and TLR9-MyD88 are driving forces of progression to HCC accompanied by liver inflammation and fibrosis in Tak1ΔHep mice. Importantly, TLR4 and TLR9 downstream TNFR, but not IL-1R signaling is crucial for the development of HCC in Tak1ΔHep mice.

Indexed as

AnimalsCarcinoma, HepatocellularHepatocytesLiver CirrhosisLiver NeoplasmsMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesMiceMice, Inbred C57BLMice, KnockoutSignal TransductionToll-Like Receptor 4Toll-Like Receptor 9MAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesTlr4 protein, mouseTlr9 protein, mouseToll-Like Receptor 4Toll-Like Receptor 9HCCliver fibrosisTAK1TNF receptor type Itoll-like receptors

Identifiers

PMID28875549
PMCPMC5790193
OpenAlexW2753074576

What OpenQuestion holds

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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.