Evidence map›Paper›PMID 24060854›Full record

ArticleJournal of hepatology2014

A novel mouse model of depletion of stellate cells clarifies their role in ischemia/reperfusion- and endotoxin-induced acute liver injury.

Rachel K Stewart, Anil Dangi, Chao Huang, Noriko Murase, Shoko Kimura, Donna B Stolz, Gregory C Wilson, Alex B Lentsch, Chandrashekhar R Gandhi

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

Article in Journal of hepatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

64 citing papers in PubMed, 111 citations in OpenAlex.

  1. Article
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  8. Expression levels of KWorld journal of experimental medicine · 2024
    Article
  9. Article
  10. Friend or foe? The elusive role of hepatic stellate cells in liver cancer.Nature reviews. Gastroenterology & hepatology · 2023
    Review
  11. Article
  12. Article
  13. Responses of hepatic sinusoidal cells to liver ischemia-reperfusion injury.Frontiers in cell and developmental biology · 2023
    Review
  14. Hepatic Stellate Cell Depletion and Genetic Manipulation.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  15. Review
  16. Review
  17. Inflammatory response to the ischaemia-reperfusion insult in the liver after major tissue trauma.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2022
    Review
  18. Article
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Rachel K Stewart *Thomas E. Starzl Transplantation Institute and Departments of Surgery, University of Pittsburgh, Pittsburgh, PA 15213.
Anil Dangi *Thomas E. Starzl Transplantation Institute and Departments of Surgery, University of Pittsburgh, Pittsburgh, PA 15213.
Chao HuangThomas E. Starzl Transplantation Institute and Departments of Surgery, University of Pittsburgh, Pittsburgh, PA 15213.
Noriko MuraseThomas E. Starzl Transplantation Institute and Departments of Surgery, University of Pittsburgh, Pittsburgh, PA 15213.
Shoko KimuraThomas E. Starzl Transplantation Institute and Departments of Surgery, University of Pittsburgh, Pittsburgh, PA 15213.
Donna B StolzDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Gregory C WilsonDepartment of Surgery University of Cincinnati and Cincinnati VA Medical Center, Cincinnati, OH, USA and Cincinnati Veterans Administration, Cincinnati, OH, USA.
Alex B LentschDepartment of Surgery University of Cincinnati and Cincinnati VA Medical Center, Cincinnati, OH, USA and Cincinnati Veterans Administration, Cincinnati, OH, USA.
Chandrashekhar R GandhiThomas E. Starzl Transplantation Institute and Departments of Surgery, University of Pittsburgh, Pittsburgh, PA 15213.
University of Pittsburgh · USUniversity of Cincinnati · US

Funding

Age Effects on Liver Inflammation and InjuryR01AG025881 · NIA · UNIVERSITY OF CINCINNATI · PI LENTSCH, ALEX B. · 2005 to 2014
$3.0M
Liver Antigen - Presenting Cells in Hepatic Injury and TransplantationP01AI081678 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI THOMSON, ANGUS W · 2009 to 2010
$2.8M
Mechanisms of Liver InjuryI01BX001174 · VA · VETERANS HEALTH ADMINISTRATION · PI GANDHI, CHANDRASHEKHAR R · 2012 to 2023
–
BLRD VA I01 BX001174NIAID NIH HHS P01 AI081678NIA NIH HHS R01 AG025881PHS HHS P01A1081678
6 · The paper itself

Abstract

BACKGROUND &

aimsHepatic stellate cells (HSCs) that express glial fibrillary acidic protein (GFAP) are located between the sinusoidal endothelial cells and hepatocytes. HSCs are activated during liver injury and cause hepatic fibrosis by producing excessive extracellular matrix. HSCs also produce many growth factors, chemokines and cytokines, and thus may play an important role in acute liver injury. However, this function has not been clarified due to unavailability of a model, in which HSCs are depleted from the normal liver.

methodsWe treated mice expressing HSV-thymidine kinase under the GFAP promoter (GFAP-Tg) with 3 consecutive (3 days apart) CCl4 (0.16 μl/g; ip) injections to stimulate HSCs to enter the cell cycle and proliferate. This was followed by 10-day ganciclovir (40 μg/g/day; ip) treatment, which is expected to eliminate actively proliferating HSCs. Mice were then subjected to hepatic ischemia/reperfusion (I/R) or endotoxin treatment.

resultsCCl4/ganciclovir treatment caused depletion of the majority of HSCs (about 64-72%), while the liver recovered from the initial CCl4-induced injury (confirmed by histology, serum ALT and neutrophil infiltration). The magnitude of hepatic injury due to I/R or endotoxemia (determined by histopathology and serum ALT) was lower in HSC-depleted mice. Their hepatic expression of TNF-α, neutrophil chemoattractant CXCL1 and endothelin-A receptor also was significantly lower than the control mice.

conclusionsHSCs play an important role both in I/R- and endotoxin-induced acute hepatocyte injury, with TNF-α and endothelin-1 as important mediators of these effects.

Indexed as

AnimalsCarbon TetrachlorideChemical and Drug Induced Liver InjuryChemokine CXCL1Disease Models, AnimalEndothelin-1GanciclovirGene ExpressionGlial Fibrillary Acidic ProteinHepatic Stellate CellsInterleukin-6LipopolysaccharidesLiverMaleMiceMice, Inbred C57BLCarbon TetrachlorideChemokine CXCL1Cxcl1 protein, mouseEndothelin-1GanciclovirGlial Fibrillary Acidic Proteinglial fibrillary astrocytic protein, mouseInterleukin-6LipopolysaccharidesNerve Tissue ProteinsThymidine KinaseTumor Necrosis Factor-alphaAbalanine aminotransferaseALTantibodyApoptosiscarbon tetrachlorideCCl(4)DepletionECMendothelin-1EndotoxemiaET-1extracellular matrixganciclovirGCVGFAPglial fibrillary acidic proteinH/Ehematoxylin and eosinhepatic stellate cellHepatic stellate cellsHepatocytesherpes simplex virusHSCHSVILInjuryinterleukinintraperitonealIPI/Rischemia/reperfusionIschemia/reperfusionKCsKupffer cellslipopolysaccharideLipopolysaccharideLiverLPSNecrosisnitric oxidenitric oxide synthaseNONOSPBSphosphate-buffered salineqRT-PCRquantitative real-time polymerase chain reactionreactive oxygen speciesROSTgthymidine kinaseTKTNFtransgenictumor necrosis factorwild typeWT

Identifiers

PMID24060854
PMCPMC4195246
OpenAlexW1974035152

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.