Evidence map›Paper›PMID 39023343›Full record

ArticleHepatology communications2024

Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure.

Sai Wang, Frederik Link, Stefan Munker, Wenjing Wang, Rilu Feng, Roman Liebe, Yujia Li, Ye Yao, Hui Liu, Chen Shao and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hepatology communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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

15 authors.

Sai WangDepartment of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID 0000-0002-9731-3948
Frederik LinkDepartment of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID 0000-0002-8384-705
Stefan MunkerDepartment of Medicine II, University Hospital, LMU Munich, Munich, Germany.
Wenjing WangBeijing Institute of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China.
Rilu FengDepartment of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Roman LiebeClinic of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University, Magdeburg, Germany.ORCID 0000-0002-3199-5595
Yujia LiDepartment of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Ye YaoDepartment of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID 0000-0001-6642-4226
Hui LiuDepartment of Pathology, Beijing You'an Hospital, Affiliated with Capital Medical University, Beijing, China.ORCID 0000-0001-8212-5285
Chen ShaoDepartment of Pathology, Beijing You'an Hospital, Affiliated with Capital Medical University, Beijing, China.
Matthias P A EbertDepartment of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID 0000-0003-3228-5138
Huiguo DingDepartment of Gastroenterology and Hepatology, Beijing You'an Hospital, Affiliated with Capital Medical University, Beijing, China.ORCID 0000-0002-8716-4926
Steven DooleyDepartment of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID 0000-0002-4840-6240
Hong-Lei WengDepartment of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID 0000-0003-1414-303
Shan-Shan WangBeijing Institute of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWhen massive necrosis occurs in acute liver failure (ALF), rapid expansion of HSCs called liver progenitor cells (LPCs) in a process called ductular reaction is required for survival. The underlying mechanisms governing this process are not entirely known to date. In ALF, high levels of retinoic acid (RA), a molecule known for its pleiotropic roles in embryonic development, are secreted by activated HSCs. We hypothesized that RA plays a key role in ductular reaction during ALF.

methodsRNAseq was performed to identify molecular signaling pathways affected by all-trans retinoid acid (atRA) treatment in HepaRG LPCs. Functional assays were performed in HepaRG cells treated with atRA or cocultured with LX-2 cells and in the liver tissue of patients suffering from ALF.

resultsUnder ALF conditions, activated HSCs secreted RA, inducing RARα nuclear translocation in LPCs. RNAseq data and investigations in HepaRG cells revealed that atRA treatment activated the WNT-β-Catenin pathway, enhanced stemness genes (SOX9, AFP, and others), increased energy storage, and elevated the expression of ATP-binding cassette transporters in a RARα nuclear translocation-dependent manner. Further, atRA treatment-induced pathways were confirmed in a coculture system of HepaRG with LX-2 cells. Patients suffering from ALF who displayed RARα nuclear translocation in the LPCs had significantly better MELD scores than those without.

conclusionsDuring ALF, RA secreted by activated HSCs promotes LPC activation, a prerequisite for subsequent LPC-mediated liver regeneration.

Indexed as

Liver Failure, AcuteStem CellsTretinoinCoculture TechniquesHepatic Stellate CellsHumansLiverRetinoic Acid Receptor alphaWnt Signaling PathwayRARA protein, humanRetinoic Acid Receptor alphaTretinoin

Identifiers

PMID39023343
PMCPMC11262820

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.