Evidence map›Paper›PMID 29037594›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017

Epigenetic Modification of MicroRNA-200b Contributes to Diabetic Vasculopathy.

Kanhaiya Singh, Durba Pal, Mithun Sinha, Subhadip Ghatak, Surya C Gnyawali, Savita Khanna, Sashwati Roy, Chandan K Sen

Open access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 6% 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

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 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

8 authors at 1 institution in 1 country.

Kanhaiya SinghDepartment of Surgery, Davis Heart and Lung Research Institute, Center for Regenerative Medicine & Cell-Based Therapies, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
Durba PalDepartment of Surgery, Davis Heart and Lung Research Institute, Center for Regenerative Medicine & Cell-Based Therapies, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
Mithun SinhaDepartment of Surgery, Davis Heart and Lung Research Institute, Center for Regenerative Medicine & Cell-Based Therapies, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
Subhadip GhatakDepartment of Surgery, Davis Heart and Lung Research Institute, Center for Regenerative Medicine & Cell-Based Therapies, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
Surya C GnyawaliDepartment of Surgery, Davis Heart and Lung Research Institute, Center for Regenerative Medicine & Cell-Based Therapies, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
Savita KhannaDepartment of Surgery, Davis Heart and Lung Research Institute, Center for Regenerative Medicine & Cell-Based Therapies, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
Sashwati RoyDepartment of Surgery, Davis Heart and Lung Research Institute, Center for Regenerative Medicine & Cell-Based Therapies, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
Chandan K SenDepartment of Surgery, Davis Heart and Lung Research Institute, Center for Regenerative Medicine & Cell-Based Therapies, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA. Electronic address: chandan.sen@osumc.edu.
The Ohio State University Wexner Medical Center · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Daniel G. Stover · 1985 to 2026
$132.3M
Coordinating and Bioinformatics Unit for the MMPC/DiaCompU24DK076169 · NIDDK · AUGUSTA UNIVERSITY · PI MCINDOE, RICHARD A. · 2006 to 2018
$42.4M
Vitamin E Neuroprotection: Novel Molecular MechanismsR01NS042617 · NINDS · OHIO STATE UNIVERSITY · PI SEN, CHANDAN K · 2002 to 2021
$3.9M
Wound Healing Endpoint and RecurrenceR01NR015676 · NINR · OHIO STATE UNIVERSITY · PI GORDILLO, GAYLE M, ROY, SASHWATI · 2015 to 2019
$2.6M
Tissue Oxygenation and Wound HealingR01GM077185 · NIGMS · OHIO STATE UNIVERSITY · PI SEN, CHANDAN K · 2007 to 2016
$2.3M
Biofilms and Immunity in Chronic WoundsR01NR013898 · NINR · OHIO STATE UNIVERSITY · PI SEN, CHANDAN K, WOZNIAK, DANIEL J · 2012 to 2016
$2.1M
iGOT neuroprotectionR01NS085272 · NINDS · OHIO STATE UNIVERSITY · PI KHANNA, SAVITA, RINK, CAMERON LUCIAN · 2013 to 2017
$1.7M
Novel Regulators of Wound AngiogenesisR01GM108014 · NIGMS · OHIO STATE UNIVERSITY · PI SEN, CHANDAN K · 2015 to 2018
$1.2M
Acquisition of a Next Generation Orbitrap MSS10OD018056 · OD · OHIO STATE UNIVERSITY · PI FREITAS, MICHAEL A. · 2014 to 2014
$573k
Mechanisms underlying impaired diabetic wound healingR56DK076566 · NIDDK · OHIO STATE UNIVERSITY · PI ROY, SASHWATI · 2016 to 2016
$347k
NCI NIH HHS P30 CA016058NIDDK NIH HHS R56 DK076566NIDDK NIH HHS U24 DK076169NIGMS NIH HHS R01 GM077185NIGMS NIH HHS R01 GM108014NIH HHS S10 OD018056NINDS NIH HHS R01 NS042617NINDS NIH HHS R01 NS085272NINR NIH HHS R01 NR013898NINR NIH HHS R01 NR015676
6 · The paper itself

Abstract

Hyperglycemia (HG) induces genome-wide cytosine demethylation. Our previous work recognized miR-200b as a critical angiomiR, which must be transiently downregulated to initiate wound angiogenesis. Under HG, miR-200b downregulation is not responsive to injury. Here, we demonstrate that HG may drive vasculopathy by epigenetic modification of a miR promoter. In human microvascular endothelial cells (HMECs), HG also lowered DNA methyltransferases (DNMT-1 and DNMT-3A) and compromised endothelial function as manifested by diminished endothelial nitric oxide (eNOS), lowered LDL uptake, impaired Matrigel tube formation, lower NO production, and compromised VE-cadherin expression. Bisulfite-sequencing documented HG-induced miR-200b promoter hypomethylation in HMECs and diabetic wound-site endothelial cells. In HMECs, HG compromised endothelial function. Methyl donor S-adenosyl-L-methionine (SAM) corrected miR-200b promoter hypomethylaton and rescued endothelial function. In vivo, wound-site administration of SAM to diabetic mice improved wound perfusion by limiting the pathogenic rise of miR-200b. Quantitative stable isotope labeling by amino acids in cell culture (SILAC) proteomics and ingenuity pathway analysis identified HG-induced proteins and principal clusters in HMECs sensitive to the genetic inhibition of miR-200b. This work presents the first evidence of the miR-200b promoter methylation as a critical determinant of diabetic wound angiogenesis.

Indexed as

Epigenesis, GeneticAnimalsCell LineDiabetes Mellitus, ExperimentalDiabetic AngiopathiesDisease Models, AnimalDNA MethylationDNA Methyltransferase 3AEndothelial CellsGene Expression RegulationHumansHyperglycemiaMiceMice, TransgenicMicroRNAsNeovascularization, PathologicadenosylselenomethionineDNA Methyltransferase 3ADNMT3A protein, humanDnmt3a protein, mouseMicroRNAsMIRN200 microRNA, humanSelenomethioninediabetic vasculopathyDNA methylationmiR-200bwound

Identifiers

PMID29037594
PMCPMC5768662
OpenAlexW2753969837

What OpenQuestion holds

Textmetadata
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.