Evidence map›Paper›PMID 28774775›Full record

ArticleVision research2017

miR-15a/16 inhibits TGF-beta3/VEGF signaling and increases retinal endothelial cell barrier proteins.

Eun-Ah Ye, Li Liu, Jena J Steinle

Open access · greenAbstract read
In one paragraph

Article in Vision research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

21 citing papers in PubMed, 37 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

3 authors at 1 institution in 1 country.

Eun-Ah YeDepartment of Anatomy and Cell Biology, Wayne State University, Detroit, MI, USA.
Li LiuDepartment of Anatomy and Cell Biology, Wayne State University, Detroit, MI, USA.
Jena J SteinleDepartment of Anatomy and Cell Biology, Wayne State University, Detroit, MI, USA; Department of Ophthalmology, Wayne State University, Detroit, MI, USA. Electronic address: jsteinle@med.wayne.edu.
Wayne State University · US

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
VISION RESEARCH--COREP30EY004068 · NEI · WAYNE STATE UNIVERSITY · PI LINDA D HAZLETT · 1985 to 2026
$13.2M
Compound 49b Prevents Retinal Endothelial Cell Death Through IGFBP-3 LevelsR01EY022045 · NEI · WAYNE STATE UNIVERSITY · PI STEINLE, JENA J · 2012 to 2016
$1.8M
NEI NIH HHS P30 EY004068NEI NIH HHS R01 EY022045NIDDK NIH HHS P30 DK020572
6 · The paper itself

Abstract

Hyperglycemia is a significant risk factor for diabetic retinopathy and induces multiple biochemical changes, including inflammation and endothelial dysfunction in the retina. Alterations in microRNA expression have been implicated in the pathological responses of diabetic retinopathy and the manipulation of microRNA may provide powerful strategy for therapeutics. Among the predicted targets of miR-15a and -16 are TGF-beta3, SMAD2/3, and VEGF, all of which are known to play a role in vascular endothelial functions. The purpose of this study was to investigate the hypothesis that miR-15a/16 inhibits TGF-beta3/VEGF signaling to maintain retinal endothelial cell barrier protein levels. Human primary retinal endothelial cells (REC) were maintained in normal (5mM) glucose or transferred to high glucose medium (25mM) for 3days. REC were transfected with miRNA mimics (hsa-miR-15a-5p and -16-5p). Retinal lysates from miR-15a-transgenic mice were also analyzed. We demonstrated that overexpression of miR-15a/16 resulted in decreased TGF-beta3 signaling and VEGF levels in cultured REC grown in high glucose conditions. In addition, the levels of tight junction proteins, zonula occludens-1 (ZO-1) and occludin, were elevated in REC following overexpression of miR-15a and -16. Overexpression of miR-15a and -16 played a role in reducing cellular permeability through inhibition of VEGF signaling in REC cultured under high glucose conditions. Using miR-15a-transgenic mice, we demonstrated the regulatory role of miR-15a on TGF-beta3 signaling and tight junction proteins in vivo. Our outcomes suggest that miR-15a/16 maintain the retinal endothelial cell barrier by reducing TGFbeta3/VEGF signaling and increasing levels of key tight junction proteins.

Indexed as

AnimalsBlotting, WesternCapillary PermeabilityCells, CulturedEndothelium, VascularGene Expression RegulationGenotyping TechniquesGlucoseHumansMiceMice, Inbred C57BLMice, TransgenicMicroRNAsOccludinRetinal VesselsSignal TransductionGlucoseMicroRNAsMirn15a microRNA, mouseMIRN15 microRNA, humanMIRN16 microRNA, humanMirn16 microRNA, mouseOccludinTight Junction ProteinsTjp1 protein, mouseTransforming Growth Factor beta3Vascular Endothelial Growth Factor Avascular endothelial growth factor A, mouseVEGFA protein, humanZonula Occludens-1 ProteinmiR-15a/16Retinal endothelial permeabilitySMAD2/3TGF-beta3VEGF

Identifiers

PMID28774775
PMCPMC5896299
OpenAlexW2743358550

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.