Evidence map›Paper›PMID 41967578›Full record

ArticleCellular and molecular gastroenterology and hepatology2026

Mesothelin/Mucin 16 Signaling in Activated Portal Fibroblasts Drives the Development of Cholestatic Fibrosis and Hepatocellular Carcinoma in Aged Female Multidrug Resistance Protein 2 Knockout Mice.

Sadatsugu Sakane, Takahiro Nishio, Hiroaki Fuji, Se Yong Park, Kei Ishizuka, Charlene Miciano, Yusuke Kimura, Mojgan Hosseini, Karin Diggle, Vivian Zhang and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Portal Fibroblasts: A Hidden Driver of Cholestasis-Associated Liver Cancer.Cellular and molecular gastroenterology and hepatology · 2026
    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

16 authors.

Sadatsugu SakaneDepartment of Medicine, University of California, San Diego, La Jolla, California; Department of Surgery, University of California, San Diego, La Jolla, California; Department of Gastroenterology and Hepatology, The University of Osaka Graduate School of Medicine, Suita, Japan.
Takahiro NishioDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Hiroaki FujiDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Se Yong ParkDepartment of Medicine, University of California, San Diego, La Jolla, California; Department of Surgery, University of California, San Diego, La Jolla, California.
Kei IshizukaDepartment of Medicine, University of California, San Diego, La Jolla, California; Department of Surgery, University of California, San Diego, La Jolla, California; Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
Charlene MicianoDepartment of Cellular and Molecular Medicine, Center for Epigenomics, University of California San Diego, La Jolla, California.
Yusuke KimuraDepartment of Medicine, University of California, San Diego, La Jolla, California; Department of Surgery, University of California, San Diego, La Jolla, California.
Mojgan HosseiniDepartment of Pathology, University of California, San Diego, La Jolla, California.
Karin DiggleDepartment of Medicine, University of California, San Diego, La Jolla, California; Department of Surgery, University of California, San Diego, La Jolla, California.
Vivian ZhangDepartment of Medicine, University of California, San Diego, La Jolla, California; Department of Surgery, University of California, San Diego, La Jolla, California.
Wonseok LeeDepartment of Medicine, University of California, San Diego, La Jolla, California; Department of Surgery, University of California, San Diego, La Jolla, California; College of Pharmacy, Gachon University, Incheon, Republic of Korea.
Hyun Young KimDepartment of Medicine, University of California, San Diego, La Jolla, California; Department of Surgery, University of California, San Diego, La Jolla, California; College of Pharmacy, Dankook University, Cheonan, Chungnam, Republic of Korea.
Xiao LiuDepartment of Medicine, University of California, San Diego, La Jolla, California; Department of Surgery, University of California, San Diego, La Jolla, California.
Allen WangDepartment of Cellular and Molecular Medicine, Center for Epigenomics, University of California San Diego, La Jolla, California.
David A BrennerDepartment of Medicine, University of California, San Diego, La Jolla, California; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California. Electronic address: dbrenner@sbpdiscovery.org.
Tatiana KisselevaDepartment of Surgery, University of California, San Diego, La Jolla, California; Sanford Stem Cell Institute, University of California, San Diego, La Jolla, California. Electronic address: tkisseleva@health.ucsd.edu.

Funding

Yeast Genetics and Stress Response Genes-BiomedicalP42ES010337 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2000 to 2022
$69.8M
The Southernearch Center for ALPD and CirrhosisP50AA011999 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ANNA S. GUKOVSKAYA · 1999 to 2026
$45.8M
San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2019 to 2026
$10.8M
Transcriptional co-regulators and macrophage gene expressionR01DK091183 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLASS, CHRISTOPHER K · 2011 to 2025
$9.9M
Inactivation of Hepatic Stellate Cells During Reversal of Liver FibrosisR01DK099205 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRENNER, DAVID A., KISSELEVA, TATIANA · 2014 to 2025
$4.8M
The Role of Portal Fibroblasts in Cholestatic Liver FibrosisR01DK101737 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA · 2014 to 2025
$3.8M
Novel IL-23 inhibitor for the treatment of alcohol associated liver diseaseU01AA029019 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA, LOOMBA, ROHIT · 2020 to 2024
$3.7M
The role of IL-17 signaling in alcohol-induced HCCR01AA028550 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRENNER, DAVID A., KISSELEVA, TATIANA · 2021 to 2025
$2.3M
Collagen fibers and fragments regulate pancreatic cancer metabolism and growth.R01CA285997 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DAVID A. BRENNER, Michael Karin · 2024 to 2026
$2.2M
Development and validation of a novel 3D human in vitro model of nonalcoholic steatohepatitis to be used for novel therapeutic screening and research on disease mechanism.R44DK115242 · NIDDK · ORGANOVO, INC. · PI MINER, JEFFREY N. · 2017 to 2019
$1.7M
Fibrocytes regulate liver fibrosisR01DK111866 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA · 2017 to 2020
$1.4M
The Role of Fibrocytes in Liver FibrosisR56DK088837 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA · 2012 to 2012
$194k
NCI NIH HHS R01 CA285997NIAAA NIH HHS P50 AA011999NIAAA NIH HHS R01 AA028550NIAAA NIH HHS U01 AA029019NIDDK NIH HHS P30 DK120515NIDDK NIH HHS R01 DK091183NIDDK NIH HHS R01 DK099205NIDDK NIH HHS R01 DK101737NIDDK NIH HHS R01 DK111866NIDDK NIH HHS R44 DK115242NIDDK NIH HHS R56 DK088837NIEHS NIH HHS P42 ES010337
6 · The paper itself

Abstract

BACKGROUND &

aimsThe contribution of activated hepatic stellate cells (aHSCs) to cholestatic fibrosis and cancer is well-documented, but the role of portal fibroblasts (PFs), and especially mesothelin (Msln)-mucin 16 (Muc16)- Thy-1 cell surface antigen (Thy-1) signaling in activated portal fibroblasts (aPFs), is unknown.

methodsThe role of aPFs/mesenchymal cells in the pathogenesis of cholestatic fibrosis and hepatocellular carcinoma (HCC) was studied in aged (16 months old) multidrug resistance protein 2 knockout (Mdr2

resultsAged female Mdr2

conclusionsThese findings demonstrate that aPFs mediate the crosstalk between cholangiocytes and hepatocytes, regulate hepatocyte functions, and that Msln-Muc16 signaling in aPFs is pathogenic for cholestatic fibrosis and HCC. Msln and Muc16 may become novel targets for anti-fibrotic therapy and patients with HCC and sclerosis cholangitis.

Indexed as

ATP Binding Cassette Transporter, Subfamily BCA-125 AntigenCarcinoma, HepatocellularCholestasisFibroblastsGPI-Linked ProteinsLiver NeoplasmsMembrane ProteinsAnimalsATP-Binding Cassette Sub-Family B Member 4Disease Models, AnimalFemaleFibrosisHumansMaleMesothelinATP-Binding Cassette Sub-Family B Member 4ATP Binding Cassette Transporter, Subfamily BCA-125 AntigenGPI-Linked ProteinsMembrane ProteinsMesothelinMsln protein, mousePdpn protein, mousePodoplaninActivated Portal FibroblastsCholestatic Liver FibrosisHepatocellular CarcinomaHepatocyte Regeneration

Identifiers

PMID41967578
PMCPMC13266261

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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.