Evidence map›Paper›PMID 29295997›Full record

ArticleNature communications2018

Diabetes impairs wound healing by Dnmt1-dependent dysregulation of hematopoietic stem cells differentiation towards macrophages.

Jinglian Yan, Guodong Tie, Shouying Wang, Amanda Tutto, Natale DeMarco, Lyne Khair, Thomas G Fazzio, Louis M Messina

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

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed, 4 pooled it
12.5field-weighted citation impact, top 1% 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

128 citing papers in PubMed, 4 syntheses or guidelines pooled it, 231 citations in OpenAlex.

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68 more citing papers are in PubMed but not listed here.

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.

Jinglian YanDiabetes Center of Excellence and Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, Worcester, MA, 01655, USA.
Guodong TieDiabetes Center of Excellence and Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, Worcester, MA, 01655, USA.
Shouying WangDiabetes Center of Excellence and Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, Worcester, MA, 01655, USA.
Amanda TuttoDiabetes Center of Excellence and Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, Worcester, MA, 01655, USA.
Natale DeMarcoDiabetes Center of Excellence and Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, Worcester, MA, 01655, USA.
Lyne KhairDiabetes Center of Excellence and Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, Worcester, MA, 01655, USA.
Thomas G FazzioDepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, 01655, USA.
Louis M MessinaDiabetes Center of Excellence and Division of Vascular and Endovascular Surgery, University of Massachusetts Medical School, Worcester, MA, 01655, USA. Louis.Messina@umassmemorial.org.
University of Massachusetts Chan Medical School · US

Funding

Hypercholesterolemia Impairs Stem Cell-Mediated Post-Ischemic NeovascularizationR01HL124101 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MESSINA, LOUIS MICHAEL · 2014 to 2017
$1.7M
NHLBI NIH HHS R01 HL124101
6 · The paper itself

Abstract

People with type 2 diabetes mellitus (T2DM) have a 25-fold higher risk of limb loss than non-diabetics due in large part to impaired wound healing. Here, we show that the impaired wound healing phenotype found in T2D mice is recapitulated in lethally irradiated wild type recipients, whose hematopoiesis is reconstituted with hematopoietic stem cells (HSCs) from T2D mice, indicating an HSC-autonomous mechanism. This impaired wound healing phenotype of T2D mice is due to a Nox-2-dependent increase in HSC oxidant stress that decreases microRNA let-7d-3p, which, in turn, directly upregulates Dnmt1, leading to the hypermethylation of Notch1, PU.1, and Klf4. This HSC-autonomous mechanism reduces the number of wound macrophages and skews their polarization towards M1 macrophages. These findings reveal a novel inflammatory mechanism by which a metabolic disorder induces an epigenetic mechanism in HSCs, which predetermines the gene expression of terminally differentiated inflammatory cells that controls their number and function.

Indexed as

Cell DifferentiationAnimalsDiabetes Mellitus, Type 2DNA (Cytosine-5-)-Methyltransferase 1DNA MethylationHematopoietic Stem CellsKruppel-Like Factor 4Kruppel-Like Transcription FactorsMacrophagesMiceMicroRNAsNADPH Oxidase 2Oxidative StressProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Receptor, Notch1Cybb protein, mouseDNA (Cytosine-5-)-Methyltransferase 1Dnmt1 protein, mouseKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsMicroRNAsmirnlet7 microRNA, mouseNADPH Oxidase 2Notch1 protein, mouseProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Receptor, Notch1Trans-Activators

Identifiers

PMID29295997
PMCPMC5750226
OpenAlexW2776403397

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.