Evidence map›Paper›PMID 37880271›Full record

ArticleScientific reports2023

PPARα activation promotes liver progenitor cell-mediated liver regeneration by suppressing YAP signaling in zebrafish.

Minwook Kim, Juhoon So, Donghun Shin

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

8 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
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  4. Review
  5. Review
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  8. Using different zebrafish models to explore liver regeneration.Frontiers in cell and developmental biology · 2024
    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

3 authors at 2 institutions in 1 country.

Minwook KimDepartment of Developmental Biology, McGowan Institute for Regenerative Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, 3501 5th Ave. #5063, Pittsburgh, PA, 15260, USA.
Juhoon SoDepartment of Developmental Biology, McGowan Institute for Regenerative Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, 3501 5th Ave. #5063, Pittsburgh, PA, 15260, USA.
Donghun ShinDepartment of Developmental Biology, McGowan Institute for Regenerative Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, 3501 5th Ave. #5063, Pittsburgh, PA, 15260, USA. donghuns@pitt.edu.
McGowan Institute for Regenerative Medicine · USUniversity of Pittsburgh · US

Funding

Elucidating the role of the FXR-PTEN-PI3K-AKT-mTOR axis in liver progenitor cell-driven liver regenerationR01DK101426 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHIN, DONGHUN · 2014 to 2023
$3.8M
Delineating Molecular Mechanisms Underlying Liver Progenitor Cell-Driven Liver RegenerationR01DK116993 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MONGA, SATDARSHAN SINGH, SHIN, DONGHUN · 2018 to 2021
$2.2M
NIDDK NIH HHS R01 DK101426NIDDK NIH HHS R01 DK116993
6 · The paper itself

Abstract

Despite the robust regenerative capacity of the liver, prolonged and severe liver damage impairs liver regeneration, leading to liver failure. Since the liver co-opts the differentiation of liver progenitor cells (LPCs) into hepatocytes to restore functional hepatocytes, augmenting LPC-mediated liver regeneration may be beneficial to patients with chronic liver diseases. However, the molecular mechanisms underlying LPC-to-hepatocyte differentiation have remained largely unknown. Using the zebrafish model of LPC-mediated liver regeneration, Tg(fabp10a:pt-β-catenin), we present that peroxisome proliferator-activated receptor-alpha (PPARα) activation augments LPC-to-hepatocyte differentiation. We found that treating Tg(fabp10a:pt-β-catenin) larvae with GW7647, a potent PPARα agonist, enhanced the expression of hepatocyte markers and simultaneously reduced the expression of biliary epithelial cell (BEC)/LPC markers in the regenerating livers, indicating enhanced LPC-to-hepatocyte differentiation. Mechanistically, PPARα activation augments the differentiation by suppressing YAP signaling. The differentiation phenotypes resulting from GW7647 treatment were rescued by expressing a constitutively active form of Yap1. Moreover, we found that suppression of YAP signaling was sufficient to promote LPC-to-hepatocyte differentiation. Treating Tg(fabp10a:pt-β-catenin) larvae with the TEAD inhibitor K-975, which suppresses YAP signaling, phenocopied the effect of GW7647 on LPC differentiation. Altogether, our findings provide insights into augmenting LPC-mediated liver regeneration as a regenerative therapy for chronic liver diseases.

Indexed as

Liver DiseasesPPAR alphaYAP-Signaling ProteinsZebrafishAnimalsbeta CateninButyratesCell ProliferationHepatocytesLiverLiver RegenerationPhenylurea CompoundsStem CellsZebrafish Proteinsbeta CateninButyratesGW 7647Phenylurea CompoundsPPAR alphaYAP-Signaling ProteinsYes-associated protein (yap), zebrafishZebrafish Proteins

Identifiers

PMID37880271
PMCPMC10600117
OpenAlexW4387950796

What Socratic 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 Socratic graph.