Evidence map›Paper›PMID 27931222›Full record

ArticleJournal of neuroinflammation2016

miR-15a/16 reduces retinal leukostasis through decreased pro-inflammatory signaling.

Eun-Ah Ye, Li Liu, Youde Jiang, Jenny Jan, Subhash Gaddipati, Susmit Suvas, Jena J Steinle

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2016. 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
2.6field-weighted citation impact, top 11% 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, 59 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

7 authors at 1 institution in 1 country.

Eun-Ah YeDepartment of Anatomy and Cell Biology, Wayne State University, 9314 Scott Hall, Detroit, MI, 48202, USA.
Li LiuDepartment of Anatomy and Cell Biology, Wayne State University, 9314 Scott Hall, Detroit, MI, 48202, USA.
Youde JiangDepartment of Anatomy and Cell Biology, Wayne State University, 9314 Scott Hall, Detroit, MI, 48202, USA.
Jenny JanDepartment of Anatomy and Cell Biology, Wayne State University, 9314 Scott Hall, Detroit, MI, 48202, USA.
Subhash GaddipatiDepartment of Anatomy and Cell Biology, Wayne State University, 9314 Scott Hall, Detroit, MI, 48202, USA.
Susmit SuvasDepartment of Anatomy and Cell Biology, Wayne State University, 9314 Scott Hall, Detroit, MI, 48202, USA.
Jena J SteinleDepartment of Anatomy and Cell Biology, Wayne State University, 9314 Scott Hall, Detroit, MI, 48202, USA. 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
Corneal neuropeptides and herpetic stromal keratitisR01EY022417 · NEI · WAYNE STATE UNIVERSITY · PI SUVAS, SUSMIT · 2013 to 2017
$1.9M
Mechanisms of TNFalpha-Induced Insulin Resistance in Retinal CellsR01EY022330 · NEI · WAYNE STATE UNIVERSITY · PI STEINLE, JENA J · 2013 to 2017
$1.5M
NEI NIH HHS P30 EY004068NEI NIH HHS R01 EY022330NEI NIH HHS R01 EY022417NIDDK NIH HHS P30 DK020572
6 · The paper itself

Abstract

backgroundHyperglycemia is a significant risk factor for diabetic retinopathy and induces increased inflammatory responses and retinal leukostasis, as well as vascular damage. Although there is an increasing amount of evidence that miRNA may be involved in the regulation in the pathology of diabetic retinopathy, the mechanisms by which miRNA mediate cellular responses to control onset and progression of diabetic retinopathy are still unclear. The purpose of our study was to investigate the hypothesis that miR-15a/16 inhibit pro-inflammatory signaling to reduce retinal leukostasis.

methodsWe generated conditional knockout mice in which miR-15a/16 are eliminated in vascular endothelial cells. For the in vitro work, human retinal endothelial cells (REC) were cultured in normal (5 mM) glucose or transferred to high glucose medium (25 mM) for 3 days. Transfection was performed on REC in high glucose with miRNA mimic (hsa-miR-15a-5p, hsa-miR-16-5p). Statistical analyses were done using unpaired Student t test with two-tailed p value. p < 0.05 was considered significant. Data are presented as mean ± SEM.

resultsWe demonstrated that high glucose conditions decreased expression of miR-15a/16 in cultured REC. Overexpression of miR-15a/16 with the mimic significantly decreased pro-inflammatory signaling of IL-1β, TNFα, and NF-κB in REC. In vivo data demonstrated that the loss of miR-15a/16 in vascular cells led to increased retinal leukostasis and CD45 levels, together with upregulated levels of IL-1β, TNFα, and NF-κB.

conclusionsThe data indicate that miR-15a/16 play significant roles in reducing retinal leukostasis, potentially through inhibition of inflammatory cellular signaling. Therefore, we suggest that miR-15a/16 offer a novel potential target for the inhibition of inflammatory mediators in diabetic retinopathy.

Indexed as

AnimalsCytokinesEndothelial CellsFlow CytometryGlucoseHumansLeukostasisMiceMice, TransgenicMicroRNAsRetinaRNA, MessengerSignal TransductionTransfectionTumor Necrosis Factor-alphaCytokinesGlucoseMicroRNAsMIRN15 microRNA, humanMIRN16 microRNA, humanRNA, MessengerTumor Necrosis Factor-alphaIL-1βLeukostasismiR-15a/16NF-κBTNFα

Identifiers

PMID27931222
PMCPMC5146897
OpenAlexW2559865118

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.