Evidence map›Paper›PMID 25076423›Full record

ArticlePloS one2014

Hepatocyte produced matrix metalloproteinases are regulated by CD147 in liver fibrogenesis.

Sarah R Calabro, Annette E Maczurek, Alison J Morgan, Thomas Tu, Victoria W Wen, Christine Yee, Auvro Mridha, Maggie Lee, William d'Avigdor, Stephen A Locarnini and 4 more

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

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.7field-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

22 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
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  6. [Reversal mechanism of hepatic fibrosis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022
    Article
  7. Article
  8. Article
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  10. CD147 promotes collective invasion through cathepsin B in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2020
    Article
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  12. 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

14 authors at 4 institutions in 1 country.

Sarah R CalabroLiver Cell Biology, Centenary Institute, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Annette E MaczurekLiver Cell Biology, Centenary Institute, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Alison J MorganLiver Cell Biology, Centenary Institute, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Thomas TuLiver Cell Biology, Centenary Institute, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Victoria W WenLiver Cell Biology, Centenary Institute, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Christine YeeLiver Cell Biology, Centenary Institute, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Auvro MridhaSydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Maggie LeeLiver Cell Biology, Centenary Institute, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
William d'AvigdorLiver Cell Biology, Centenary Institute, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Stephen A LocarniniVictorian Infectious Disease Laboratory, Melbourne, VIC, Australia.
Geoffrey W McCaughanSydney Medical School, The University of Sydney, Sydney, NSW, Australia; A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia; Liver Injury and Cancer, Centenary Institute, Sydney, NSW, Australia.
Fiona J WarnerLiver Cell Biology, Centenary Institute, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Susan V McLennanSydney Medical School, The University of Sydney, Sydney, NSW, Australia; Department of Endocrinology, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia.
Nicholas A ShackelLiver Cell Biology, Centenary Institute, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia.
University of Sydney · AUCentenary Institute · AURoyal Prince Alfred Hospital · AUVictorian Infectious Diseases Reference Laboratory · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe classical paradigm of liver injury asserts that hepatic stellate cells (HSC) produce, remodel and turnover the abnormal extracellular matrix (ECM) of fibrosis via matrix metalloproteinases (MMPs). In extrahepatic tissues MMP production is regulated by a number of mechanisms including expression of the glycoprotein CD147. Previously, we have shown that CD147 is expressed on hepatocytes but not within the fibrotic septa in cirrhosis [1]. Therefore, we investigated if hepatocytes produce MMPs, regulated by CD147, which are capable of remodelling fibrotic ECM independent of the HSC.

methodsNon-diseased, fibrotic and cirrhotic livers were examined for MMP activity and markers of fibrosis in humans and mice. CD147 expression and MMP activity were co-localised by in-situ zymography. The role of CD147 was studied in-vitro with siRNA to CD147 in hepatocytes and in-vivo in mice with CCl4 induced liver injury using ãCD147 antibody intervention.

resultsIn liver fibrosis in both human and mouse tissue MMP expression and activity (MMP-2, -9, -13 and -14) increased with progressive injury and localised to hepatocytes. Additionally, as expected, MMPs were abundantly expressed by activated HSC. Further, with progressive fibrosis there was expression of CD147, which localised to hepatocytes but not to HSC. Functionally significant in-vitro regulation of hepatocyte MMP production by CD147 was demonstrated using siRNA to CD147 that decreased hepatocyte MMP-2 and -9 expression/activity. Further, in-vivo α-CD147 antibody intervention decreased liver MMP-2, -9, -13, -14, TGF-β and α-SMA expression in CCl4 treated mice compared to controls.

conclusionWe have shown that hepatocytes produce active MMPs and that the glycoprotein CD147 regulates hepatocyte MMP expression. Targeting CD147 regulates hepatocyte MMP production both in-vitro and in-vivo, with the net result being reduced fibrotic matrix turnover in-vivo. Therefore, CD147 regulation of hepatocyte MMP is a novel pathway that could be targeted by future anti-fibrogenic agents.

Indexed as

AnimalsBasiginCells, CulturedChemical and Drug Induced Liver InjuryHepatocytesHumansHydrocarbons, BrominatedImmunohistochemistryLiverLiver CirrhosisMatrix Metalloproteinase 2Matrix Metalloproteinase 9Matrix MetalloproteinasesMiceMice, Inbred BALB CMice, Inbred C57BLBasigincarbon tetrabromideHydrocarbons, BrominatedMatrix Metalloproteinase 2Matrix Metalloproteinase 9Matrix MetalloproteinasesRNA, Small InterferingTissue Inhibitor of Metalloproteinases

Identifiers

PMID25076423
PMCPMC4116334
OpenAlexW1997457418

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.