Evidence map›Paper›PMID 36371458›Full record

ArticleScientific reports2022

Epithelial membrane protein 2 (EMP2) regulates hypoxia-induced angiogenesis in the adult retinal pigment epithelial cell lines.

Michel Sun, Nina Cherian, Lucia Liu, Ann M Chan, Brian Aguirre, Alison Chu, Jason Strawbridge, Esther S Kim, Meng-Chin Lin, Irena Tsui and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 32% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
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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 1 institution in 1 country.

Michel SunUCLA Stein Eye Institute and the Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Nina CherianUCLA Stein Eye Institute and the Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Lucia LiuDepartment of Pathology Lab Medicine, 4525 MacDonald Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Ann M ChanUCLA Stein Eye Institute and the Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Brian AguirreDepartment of Pathology Lab Medicine, 4525 MacDonald Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Alison ChuDivision of Neonatology and Developmental Biology, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Jason StrawbridgeUCLA Stein Eye Institute and the Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Esther S KimDivision of Neonatology and Developmental Biology, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Meng-Chin LinDivision of Neonatology and Developmental Biology, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Irena TsuiUCLA Stein Eye Institute and the Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Lynn K GordonUCLA Stein Eye Institute and the Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Madhuri WadehraDepartment of Pathology Lab Medicine, 4525 MacDonald Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. mwadehra@mednet.ucla.edu.
University of California, Los Angeles · US

Funding

Vision Science Training ProgramT32EY007026 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Alapakkam P Sampath · 1985 to 2026
$5.7M
Targeting epithelial membrane protein 2 (EMP2) in retinopathy of prematurityR01EY032561 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHU, ALISON · 2021 to 2025
$2.0M
NEI NIH HHS R01 EY032561NEI NIH HHS T32 EY007026
6 · The paper itself

Abstract

Pathologic retinal neovascularization is a potentially blinding consequence seen in many common diseases including diabetic retinopathy, retinopathy of prematurity, and retinal vaso-occlusive diseases. This study investigates epithelial membrane protein 2 (EMP2) and its role as a possible modulator of angiogenesis in human retinal pigment epithelium (RPE) under hypoxic conditions. To study its effects, the RPE cell line ARPE-19 was genetically modified to either overexpress EMP2 or knock down its levels, and RNA sequencing and western blot analysis was performed to confirm the changes in expression at the RNA and protein level, respectively. Protein expression was evaluated under both normoxic conditions or hypoxic stress. Capillary tube formation assays with human umbilical vein endothelial cells (HUVEC) were used to evaluate functional responses. EMP2 expression was found to positively correlate with expression of pro-angiogenic factors HIF1α and VEGF at both mRNA and protein levels under hypoxic conditions. Mechanistically, EMP2 stabilized HIF1α expression through downregulation of von Hippel Lindau protein (pVHL). EMP2 mediated changes in ARPE-19 cells were also found to alter the secretion of a paracrine factor(s) in conditioned media that can regulate HUVEC migration and capillary tube formation in in vitro functional angiogenesis assays. This study identifies EMP2 as a potential mediator of angiogenesis in a human RPE cell line. EMP2 levels positively correlate with pro-angiogenic mediators HIF1α and VEGF, and mechanistically, EMP2 regulates HIF1α through downregulation of pVHL. This study supports further investigation of EMP2 as a promising novel target for therapeutic treatment of pathologic neovascularization in the retina.

Indexed as

Neovascularization, PathologicVascular Endothelial Growth Factor AHumansHuman Umbilical Vein Endothelial CellsHypoxiaInfant, NewbornMembrane GlycoproteinsMembrane ProteinsRetinal Pigment EpitheliumRetinal PigmentsEMP2 protein, humanMembrane GlycoproteinsMembrane ProteinsRetinal PigmentsVascular Endothelial Growth Factor A

Identifiers

PMID36371458
PMCPMC9653491
OpenAlexW4309074940

What OpenQuestion holds

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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 OpenQuestion graph.