Evidence map›Paper›PMID 19515996›Full record

ArticleInvestigative ophthalmology & visual science2009

Zeb1 represses Mitf and regulates pigment synthesis, cell proliferation, and epithelial morphology.

Yongqing Liu, Fei Ye, Qiutang Li, Shigeo Tamiya, Douglas S Darling, Henry J Kaplan, Douglas C Dean

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

34 citing papers in PubMed, 58 citations in OpenAlex.

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  14. Yap1 is required for maintenance of adult RPE differentiation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
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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

7 authors at 1 institution in 1 country.

Yongqing LiuJames Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA.
Fei Ye
Qiutang Li
Shigeo Tamiya
Douglas S Darling
Henry J Kaplan
Douglas C Dean
Stem Cell Institute · PA

Funding

PROJ 12: STEM CELL-BASED VACCINE FOR CANCER PROPHYLAXISP20RR018733 · NCRR · UNIVERSITY OF LOUISVILLE · PI LI, QIUTANG · 2003 to 2011
$18.9M
Vision Research Infrastructure DevelopmentR24EY015636 · NEI · UNIVERSITY OF LOUISVILLE · PI KAPLAN, HENRY JERROLD · 2004 to 2008
$1.0M
Ocular defects caused by TCF8/Zfhx1a mutationsR21EY017869 · NEI · UNIVERSITY OF LOUISVILLE · PI DARLING, DOUGLAS S · 2007 to 2008
$403k
NCRR NIH HHS P20 RR018733NEI NIH HHS EY015636NEI NIH HHS EY017869NEI NIH HHS R21 EY017869NEI NIH HHS R24 EY015636
6 · The paper itself

Abstract

purposeEpithelial-mesenchymal transition (EMT) is important in fibrotic responses, formation of cancer stem cells, and acquisition of a metastatic phenotype. Zeb1 represses epithelial specification genes to enforce epithelial-mesenchymal phenotypic boundaries during development, and it is one of several E-box-binding repressors whose overexpression triggers EMT. The purpose of this study was to investigate the potential role for Zeb1 in EMT leading to the dedifferentiation of retinal pigment epithelial (RPE) cells.

methodsReal-time PCR was used to examine mRNA expression during RPE dedifferentiation in primary cultures of RPE cells from Zeb1(+/-) mice and after knockdown of Zeb1 by lentivirus shRNA. Chromatin immunoprecipitation was used to detect Zeb1 at gene promoters in vivo.

resultsZeb1 is overexpressed during RPE dedifferentiation. Heterozygous mutation or shRNA knockdown to prevent this overexpression eliminates the onset of proliferation, loss of epithelial morphology, and pigment, which characterizes RPE dedifferentiation. Zeb1 binds to the Mitf A promoter in vivo, and Zeb1 mutation or shRNA knockdown derepresses the gene. The authors link Zeb1 expression to cell-cell contact and demonstrate that forcing dedifferentiated RPE cells to adopt cell-cell only contacts via sphere formation reverses the overexpression of Zeb1 and reprograms RPE cells back to a pigmented phenotype.

conclusionsOverexpression of the EMT transcription factor Zeb1 has an important role in RPE dedifferentiation via its regulation of Mitf. Expression of Zeb1 and, in turn, RPE dedifferentiation, is linked to cell-cell contact, and these contacts can be used to diminish Zeb1 expression and reprogram dedifferentiated RPE cells.

Indexed as

Cell ProliferationAnimalsAnimals, NewbornCell DifferentiationCells, CulturedCyclin-Dependent Kinase Inhibitor p21Down-RegulationEpithelial CellsGene Expression RegulationGene Knockout TechniquesHomeodomain ProteinsKruppel-Like Transcription FactorsMelaninsMesodermMiceMice, Inbred C57BLCdkn1a protein, mouseCyclin-Dependent Kinase Inhibitor p21Homeodomain ProteinsKruppel-Like Transcription FactorsMelaninsMicrophthalmia-Associated Transcription FactorMitf protein, mouseRNA, MessengerZEB1 protein, mouseZinc Finger E-box-Binding Homeobox 1

Identifiers

PMID19515996
PMCPMC3648851
OpenAlexW1968772250

What OpenQuestion holds

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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.