Evidence map›Paper›PMID 30358115›Full record

ArticleLiver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society2019

Overproduction of Tenascin-C Driven by Lipid Accumulation in the Liver Aggravates Hepatic Ischemia/Reperfusion Injury in Steatotic Mice.

Hiroyuki Kato, Sergio Duarte, Mary G Miller, Ronald W Busuttil, Ana J Coito

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

Article in Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 23% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
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  4. Article
  5. Tenascin-C induction exacerbates post-stroke brain damage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022
    Article
  6. Article
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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.

Hiroyuki KatoThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA.
Sergio DuarteThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA.
Mary G MillerThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA.
Ronald W BusuttilThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA.ORCID 0000-0001-8157-1531
Ana J CoitoThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA.
University of California, Los Angeles · US

Funding

Matrix Metalloproteinases in Hepatic Ischemia and Reperfusion InjuryR01AI057832 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COITO, ANA J. · 2004 to 2014
$3.5M
NIAID NIH HHS R01 AI057832
6 · The paper itself

Abstract

The purpose of this study was to assess the significance of tenascin-C (Tnc) expression in steatotic liver ischemia/reperfusion injury (IRI). The critical shortage in donor organs has led to the use of steatotic livers in transplantation regardless of their elevated susceptibility to hepatic IRI. Tnc is an endogenous danger signal extracellular matrix molecule involved in various aspects of immunity and tissue injury. In the current study, mice were fed with a steatosis-inducing diet and developed approximately 50% hepatic steatosis, predominantly macrovesicular, before being subjected to hepatic IRI. We report here that lipid accumulation in hepatocytes inflated the production of Tnc in steatotic livers and in isolated hepatic stellate cells. Moreover, we show that the inability of Tnc-/- deficient steatotic mice to express Tnc significantly protected these mice from liver IRI. Compared with fatty controls, Tnc-/- steatotic mice showed significantly reduced serum transaminase levels and enhanced liver histological preservation at both 6 and 24 hours after hepatic IRI. The lack of Tnc expression resulted in impaired lymphocyte antigen 6 complex, locus (Ly6G) neutrophil and macrophage antigen-1 (Mac-1) leukocyte recruitment as well as in decreased expression of proinflammatory mediators (interleukin 1β, tumor necrosis factor α, and chemokine [C-X-C motif] ligand 2) after liver reperfusion. Myeloperoxidase (MPO) is the most abundant cytotoxic enzyme secreted by neutrophils and a key mediator of neutrophil-induced oxidative tissue injuries. Using an in vitro model of steatosis, we also show that Tnc markedly potentiated the effect of steatotic hepatocytes on neutrophil-derived MPO activity. In conclusion, our data support the view that inhibition of Tnc is a promising therapeutic approach to lessen inflammation in steatotic livers and to maximize their successful use in organ transplantation.

Indexed as

AllograftsAnimalsDisease Models, AnimalDonor SelectionExtracellular MatrixHepatocytesHumansInflammation MediatorsLipid MetabolismLiverLiver Function TestsLiver TransplantationMaleMiceMice, KnockoutNon-alcoholic Fatty Liver DiseaseInflammation MediatorsTenascinTnc protein, mouse

Identifiers

PMID30358115
PMCPMC6355355
OpenAlexW2898576858

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.