Evidence map›Paper›PMID 28187190›Full record

ArticlePloS one2017

Widespread GLI expression but limited canonical hedgehog signaling restricted to the ductular reaction in human chronic liver disease.

Candice Alexandra Grzelak, Nicholas David Sigglekow, Janina Elke Eleonore Tirnitz-Parker, Elizabeth Jane Hamson, Alessandra Warren, Bharvi Maneck, Jinbiao Chen, Bramilla Patkunanathan, Jade Boland, Robert Cheng and 6 more

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

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 35% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. The hedgehog pathway in nonalcoholic fatty liver disease.Critical reviews in biochemistry and molecular biology · 2018
    Review
  6. 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

16 authors at 5 institutions in 2 countries.

Candice Alexandra GrzelakLiver Injury and Cancer, Centenary Institute, Camperdown, New South Wales, Australia.ORCID http://orcid.org/0000-0001-8645-4297
Nicholas David SigglekowLiver Injury and Cancer, Centenary Institute, Camperdown, New South Wales, Australia.
Janina Elke Eleonore Tirnitz-ParkerSchool of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, Australia.
Elizabeth Jane HamsonLiver Injury and Cancer, Centenary Institute, Camperdown, New South Wales, Australia.
Alessandra WarrenAgeing and Alzheimers Institute, Centre for Education and Research on Ageing, University of Sydney, Concord Hospital, Sydney, New South Wales, Australia.
Bharvi ManeckLiver Injury and Cancer, Centenary Institute, Camperdown, New South Wales, Australia.
Jinbiao ChenLiver Injury and Cancer, Centenary Institute, Camperdown, New South Wales, Australia.
Bramilla PatkunanathanLiver Injury and Cancer, Centenary Institute, Camperdown, New South Wales, Australia.
Jade BolandLiver Injury and Cancer, Centenary Institute, Camperdown, New South Wales, Australia.
Robert ChengLiver Injury and Cancer, Centenary Institute, Camperdown, New South Wales, Australia.
Nicholas Adam ShackelLiver Injury and Cancer, Centenary Institute, Camperdown, New South Wales, Australia.
Devanshi SethLiver Injury and Cancer, Centenary Institute, Camperdown, New South Wales, Australia.
David Geoffrey BowenLiver Injury and Cancer, Centenary Institute, Camperdown, New South Wales, Australia.
Luciano Gastón MartelottoDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
D Neil WatkinsThe Kinghorn Cancer Centre, Garvan Institute, Darlinghurst, New South Wales, Australia.
Geoffrey William McCaughanLiver Injury and Cancer, Centenary Institute, Camperdown, New South Wales, Australia.
Centenary Institute · AUThe University of Sydney · AUCurtin University · AUGarvan Institute of Medical Research · AUMemorial Sloan Kettering Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations. This study extends these observations to human liver tissue, and analyses the effect of GLI inhibition on LPC viability/gene expression. Human donor and cirrhotic liver tissue specimens were evaluated for SHH, GLI2 and Pc expression using immunofluorescence and qRT-PCR. Changes to viability and gene expression in LPCs in vitro were assessed following GLI inhibition. Identification of Pc (as a marker of canonical Hh signaling) in human cirrhosis was predominantly confined to the ductular reaction and LPCs. In contrast, GLI2 was expressed in multiple cell populations including Pc-ve endothelium, hepatocytes, and leukocytes. HSCs/myofibroblasts (>99%) expressed GLI2, with only 1.92% displaying Pc. In vitro GLI signals maintained proliferation/viability within LPCs and GLI inhibition affected the expression of genes related to stemness, hepatocyte/biliary differentiation and Hh/Wnt signaling. At least two mechanisms of GLI signaling (Pc/SMO-dependent and Pc/SMO-independent) mediate chronic liver disease pathogenesis. This may have significant ramifications for the choice of Hh inhibitor (anti-SMO or anti-GLI) suitable for clinical trials. We also postulate GLI delivers a pro-survival signal to LPCs whilst maintaining stemness.

Indexed as

Signal TransductionAdultAgedCiliaEndotheliumFemaleHedgehog ProteinsHepatocytesHumansKruppel-Like Transcription FactorsLeukocytesLiver DiseasesMaleMiddle AgedNuclear ProteinsZinc Finger Protein Gli2GLI2 protein, humanHedgehog ProteinsKruppel-Like Transcription FactorsNuclear ProteinsSHH protein, humanZinc Finger Protein Gli2

Identifiers

PMID28187190
PMCPMC5302813
OpenAlexW2587449237

What Socratic holds

Textmetadata
LicenceCC0
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 Socratic graph.