Evidence map›Paper›PMID 25490205›Full record

ArticlePloS one2014

Targeting miR-146a to treat delayed wound healing in human diabetic organ-cultured corneas.

Michael A Winkler, Christian Dib, Alexander V Ljubimov, Mehrnoosh Saghizadeh

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

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 4% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

  1. Pooled it
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  17. Corneal Epithelial Regeneration: Old and New Perspectives.International journal of molecular sciences · 2022
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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

4 authors at 2 institutions in 1 country.

Michael A WinklerEye Program, Board of Governors Regenerative Medicine Institute, Departments of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Christian DibEye Program, Board of Governors Regenerative Medicine Institute, Departments of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States of America; David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
Alexander V LjubimovEye Program, Board of Governors Regenerative Medicine Institute, Departments of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States of America; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, United States of America; David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
Mehrnoosh SaghizadehEye Program, Board of Governors Regenerative Medicine Institute, Departments of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States of America; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, United States of America; David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
Cedars-Sinai Medical Center · USUniversity of California, Los Angeles · US

Funding

Mechanisms of Epithelial Alterations in Diabetic CorneaR01EY013431 · NEI · CEDARS-SINAI MEDICAL CENTER · PI Alexander V Ljubimov · 2001 to 2026
$11.3M
The Role of MicroRNAs in Normal and Diseased Corneal Epithelial HomeostasisR01EY025377 · NEI · CEDARS-SINAI MEDICAL CENTER · PI Mehrnoosh Saghizadeh Ghiam · 2015 to 2026
$4.3M
The Role and Mechanisms of microRNAs in Diabetic CorneaR21EY022771 · NEI · CEDARS-SINAI MEDICAL CENTER · PI GHIAM, MEHRNOOSH SAGHIZADEH · 2012 to 2013
$443k
NEI NIH HHS R01 EY013431NEI NIH HHS R01 EY025377NEI NIH HHS R01 EY13431NEI NIH HHS R21 EY022771
6 · The paper itself

Abstract

Limbal epithelial stem cells (LESC) residing at the corneal periphery are largely responsible for maintaining corneal optical transparency by continuously supplying new corneal epithelial cells, which mature during their radial migration to the central cornea. Diabetes mellitus (DM) affects all the structures of the eye including the cornea. Frequent epithelial erosions, delayed wound healing, and microbial infections are common alterations of the diabetic eye that can result in vision loss. MicroRNAs (miRNAs) are short non-coding oligonucleotides that regulate gene expression by repressing translation. Our purpose was to understand the role of miR-146a in the human limbal versus central corneal epithelial compartment in normal and pathological conditions such as diabetes mellitus. Using quantitative real-time PCR (QPCR) we found miR-146a enrichment in the limbal corneal compartment. This miRNA was also expressed at higher levels in the diabetic vs. normal limbus. Cell migration and wound closure were significantly delayed in normal and diabetic primary limbal epithelial cells (LEC) transfected with miR-146a. Cells treated with miR-146a had decreased levels of phosphorylated (activated) p38 and EGFR, mediators of epithelial wound healing. Conversely, inhibition of miR-146a significantly enhanced cell migration in both normal and diabetic primary LEC and in diabetic organ-cultured corneas by nearly 40% vs. scrambled miRNA control, accompanied by increased phosphorylated signaling intermediates. Transfection of miR-146a in cultured LEC resulted in an increased immunoreactivity for putative LEC markers Frizzled-7 and K15, whereas inhibition of miR-146a decreased their expressions. These data suggest that miR-146a plays a role in LEC maintenance at the corneal periphery, and its expression is downregulated during their migration towards the central cornea and accompanying terminal differentiation. Furthermore, abnormal miR-146a upregulation may be an important mechanism of delayed wound healing in the diabetic cornea.

Indexed as

Cell MovementCell ProliferationCells, CulturedCorneaDiabetes ComplicationsErbB ReceptorsGene Expression RegulationHumansMicroRNAsp38 Mitogen-Activated Protein KinasesPhosphorylationReal-Time Polymerase Chain ReactionStem CellsWound HealingEGFR protein, humanErbB ReceptorsMicroRNAsMIRN146 microRNA, humanp38 Mitogen-Activated Protein Kinases

Identifiers

PMID25490205
PMCPMC4260878
OpenAlexW2074837243

What OpenQuestion holds

Textmetadata
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.