Evidence map›Paper›PMID 32244897›Full record

ArticlePharmaceutics2020

Design of a Gene Panel to Expose the Versatile Role of Hepatic Stellate Cells in Human Liver Fibrosis.

Fransien van Dijk, Christa M Hazelhoff, Eduard Post, Gerian G H Prins, Krista Rombouts, Klaas Poelstra, Peter Olinga, Leonie Beljaars

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

Article in Pharmaceutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 33% 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

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Best Practices and Progress in Precision-Cut Liver Slice Cultures.International journal of molecular sciences · 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

8 authors at 2 institutions in 2 countries.

Fransien van DijkGroningen Research Institute of Pharmacy, Department of Pharmacokinetics, Toxicology and Targeting, University of Groningen, 9713 AV Groningen, The Netherlands.
Christa M HazelhoffGroningen Research Institute of Pharmacy, Department of Pharmacokinetics, Toxicology and Targeting, University of Groningen, 9713 AV Groningen, The Netherlands.
Eduard PostGroningen Research Institute of Pharmacy, Department of Pharmacokinetics, Toxicology and Targeting, University of Groningen, 9713 AV Groningen, The Netherlands.
Gerian G H PrinsGroningen Research Institute of Pharmacy, Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 AV Groningen, The Netherlands.ORCID 0000-0002-7225-9076
Krista RomboutsUCL Institute for Liver and Digestive Health, University College London Division of Medicine, London NW3 2PF , UK.ORCID 0000-0001-9440-0571
Klaas PoelstraGroningen Research Institute of Pharmacy, Department of Pharmacokinetics, Toxicology and Targeting, University of Groningen, 9713 AV Groningen, The Netherlands.
Peter OlingaGroningen Research Institute of Pharmacy, Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 AV Groningen, The Netherlands.ORCID 0000-0003-4855-8452
Leonie BeljaarsGroningen Research Institute of Pharmacy, Department of Pharmacokinetics, Toxicology and Targeting, University of Groningen, 9713 AV Groningen, The Netherlands.ORCID 0000-0003-3659-1896
University of Groningen · NLUniversity College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The pivotal cell involved in the pathogenesis of liver fibrosis, i.e., the activated hepatic stellate cell (HSC), has a wide range of activities during the initiation, progression and even regression of the disease. These HSC-related activities encompass cellular activation, matrix synthesis and degradation, proliferation, contraction, chemotaxis and inflammatory signaling. When determining the in vitro and in vivo effectivity of novel antifibrotic therapies, the readout is currently mainly based on gene and protein levels of α-smooth muscle actin (α-SMA) and the fibrillar collagens (type I and III). We advocate for a more comprehensive approach in addition to these markers when screening potential antifibrotic drugs that interfere with HSCs. Therefore, we aimed to develop a gene panel for human in vitro and ex vivo drug screening models, addressing each of the HSC-activities with at least one gene, comprising, in total, 16 genes. We determined the gene expression in various human stellate cells, ranging from primary cells to cell lines with an HSC-origin, and human liver slices and stimulated them with two key profibrotic factors, i.e., transforming growth factor β (TGFβ) or platelet-derived growth factor BB (PDGF-BB). We demonstrated that freshly isolated HSCs showed the strongest and highest variety of responses to these profibrotic stimuli, in particular following PDGF-BB stimulation, while cell lines were limited in their responses. Moreover, we verified these gene expression profiles in human precision-cut liver slices and showed similarities with the TGFβ- and PDGF-BB-related fibrotic responses, as observed in the primary HSCs. With this study, we encourage researchers to get off the beaten track when testing antifibrotic compounds by including more HSC-related markers in their future work. This way, potential compounds will be screened more extensively, which might increase the likelihood of developing effective antifibrotic drugs.

Indexed as

drug developmentfibrosis gene panelmyofibroblastplatelet-derived growth factor BBprecision-cut liver slicesprimary hepatic stellate cellsreversiontransforming growth factor β

Identifiers

PMID32244897
PMCPMC7151042
OpenAlexW3012457339

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.