Evidence map›Paper›PMID 21779369›Full record

ArticlePloS one2011

Transgenic overexpression of Tcfap2c/AP-2gamma results in liver failure and intestinal dysplasia.

Daniel Holl, Peter Kuckenberg, Tatiana Woynecki, Angela Egert, Astrid Becker, Sebastian Huss, Dirk Stabenow, Andreas Zimmer, Percy Knolle, René Tolba and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.1field-weighted citation impact, top 47% 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

7 citing papers in PubMed, 21 citations in OpenAlex.

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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

12 authors at 2 institutions in 1 country.

Daniel HollDepartment of Developmental Pathology, Institute of Pathology, University of Bonn Medical School, Bonn, Germany.
Peter Kuckenberg
Tatiana Woynecki
Angela Egert
Astrid Becker
Sebastian Huss
Dirk Stabenow
Andreas Zimmer
Percy Knolle
René Tolba
Hans-Peter Fischer
Hubert Schorle
University of Bonn · DERWTH Aachen University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe transcription factor Tcfap2c has been demonstrated to be essential for various processes during mammalian development. It has been found to be upregulated in various undifferentiated tumors and is implicated with poor prognosis. Tcfap2c is reported to impinge on cellular proliferation, differentiation and apoptosis. However, the physiological consequences of Tcfap2c-expression remain largely unknown. METHODOLOGY/PRINCIPAL

findingsTherefore we established a gain of function model to analyze the role of Tcfap2c in development and disease. Induction of the transgene led to robust expression in all tissues (except brain and testis) and lead to rapid mortality within 3-7 days. In the liver cellular proliferation and apoptosis was detected. Accumulation of microvesicular lipid droplets and breakdown of major hepatic metabolism pathways resulted in steatosis. Serum analysis showed a dramatic increase of enzymes indicative for hepatic failure. After induction of Tcfap2c we identified a set of 447 common genes, which are deregulated in both liver and primary hepatocyte culture. Further analysis showed a prominent repression of the cytochrome p450 system, PPARA, Lipin1 and Lipin2. These data indicate that in the liver Tcfap2c represses pathways, which are responsible for fatty acid metabolism. In the intestine, Tcfap2c expression resulted in expansion of Sox9 positive and proliferative active epithelial progenitor cells resulting in dysplastic growth of mucosal crypt cells and loss of differentiated mucosa.

conclusionsThe transgenic mice show that ectopic expression of Tcfap2c is not tolerated. Due to the phenotype observed, iTcfap2c-mice represent a model system to study liver failure. In intestine, Tcfap2c induced cellular hyperplasia and suppressed terminal differentiation indicating that Tcfap2c serves as a repressor of differentiation and inducer of proliferation. This might be achieved by the Tcfap2c mediated activation of Sox9 known to be expressed in intestinal and hepatic stem/progenitor cell populations.

Indexed as

AnimalsBlotting, WesternCell ProliferationCells, CulturedIntestinal DiseasesLipid MetabolismLiver FailureMiceMice, TransgenicMicroscopy, Electron, TransmissionNuclear ProteinsOligonucleotide Array Sequence AnalysisPhosphatidate PhosphatasePPAR alphaReverse Transcriptase Polymerase Chain ReactionTranscription Factor AP-2Lipin 2 protein, mouseLpin1 protein, mouseNuclear ProteinsPhosphatidate PhosphatasePPAR alphaTfap2c protein, mouseTranscription Factor AP-2

Identifiers

PMID21779369
PMCPMC3135619
OpenAlexW2069994876

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Registered trials

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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.