Evidence map›Paper›PMID 36946436›Full record

ArticleJournal of cellular biochemistry2023

Tyrosine phosphorylation of YAP-1 in biliary epithelial cells mediates posthepatectomy liver regeneration and is affected by serotonin.

Patrick Starlinger, Laura Brunnthaler, Ryan Watkins, David Pereyra, Judith Stift, Michaela Finsterbusch, Jonas Santol, Thomas Gruenberger, Alice Assinger, Rory Smoot

Open access · hybridAbstract read
In one paragraph

Article in Journal of cellular biochemistry, 2023. 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
0.4field-weighted citation impact, top 39% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Modulation of the Mechanosensory Matrisome by Serotonergic Signaling.Results and problems in cell differentiation · 2026
    Review
  2. 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

10 authors at 4 institutions in 2 countries.

Patrick StarlingerDepartment of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Minnesota, Rochester, USA.ORCID 0000-0002-4666-5337
Laura BrunnthalerCenter of Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
Ryan WatkinsDepartment of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Minnesota, Rochester, USA.
David PereyraDepartment of Surgery, General Hospital, Medical University of Vienna, Vienna, Austria.
Judith StiftClinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
Michaela FinsterbuschCenter of Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
Jonas SantolDepartment of Surgery, General Hospital, Medical University of Vienna, Vienna, Austria.
Thomas GruenbergerDepartment of Surgery, HPB Center, Viennese Health Network, Clinic Favoriten and Sigmund Freud Private University, Vienna, Austria.
Alice AssingerCenter of Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
Rory SmootDepartment of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Minnesota, Rochester, USA.ORCID 0000-0001-8543-661X
Medical University of Vienna · ATMayo Clinic · USVienna General Hospital · ATSigmund Freud Privatuniversität Wien · AT

Funding

Novel coagulation-dependent mechanisms of liver regeneration to detect and prevent liver dysfunction after partial hepatectomyR01DK122813 · NIDDK · MICHIGAN STATE UNIVERSITY · PI LUYENDYK, JAMES P · 2020 to 2024
$2.0M
Austrian Science Fund FWF P 32064NIDDK NIH HHS R01 DK122813NIH HHS R01DK122813
6 · The paper itself

Abstract

Experimental data suggested activation of yes-associated protein (YAP-1) as a critical regulator of liver regeneration (LR). Serotonin (5-HT) promotes LR in rodent models and has been proposed to act via YAP-1. How 5-HT affects LR is incompletely understood. A possible mechanism how 5-HT affects human LR was explored. Sixty-one patients were included. Tissue samples prior and 2 h after induction of LR were collected. Circulating levels of 5-HT and osteopontin (OPN) were assessed. YAP-1, its phosphorylation states, cytokeratin 19 (CK-19) and OPN were assessed using immunofluorescence. A mouse model of biliary epithelial cells (BECs) specific deletion of YAP/TAZ was developed. YAP-1 increased as early as 2 h after induction of LR (p = 0.025) predominantly in BECs. BEC specific deletion of YAP/TAZ reduced LR after 70% partial hepatectomy in mice (Ki67%, p < 0.001). SSRI treatment, depleting intra-platelet 5-HT, abolished YAP-1 and OPN induction upon LR. Portal vein 5-HT levels correlated with intrahepatic YAP-1 expression upon LR (R = 0.703, p = 0.035). OPN colocalized with YAP-1 in BECs and its circulating levels increased in the liver vein 2 h after induction of LR (p = 0.017). In the context of LR tyrosine-phosphorylated YAP-1 significantly increased (p = 0.042). Stimulating BECs with 5-HT resulted in increased YAP-1 activation via tyrosine-phosphorylation and subsequently increased OPN expression. BECs YAP-1 appears to be critical for LR in mice and humans. Our evidence suggests that 5-HT, at least in part, exerts its pro-regenerative effects via YAP-1 tyrosine-phosphorylation in BECs and subsequent OPN-dependent paracrine immunomodulation.

Indexed as

Liver RegenerationSerotoninAnimalsCell ProliferationEpithelial CellsHumansLiverMicePhosphorylationTyrosineYAP-Signaling ProteinsSerotoninTyrosineYAP1 protein, humanYap1 protein, mouseYAP-Signaling Proteinsliver regenerationosteopontinserotonintyrosine phosphorylationYAP-1

Identifiers

PMID36946436
PMCPMC10200759
OpenAlexW4353015411

What OpenQuestion holds

Textmetadata
LicenceTDM
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.