Evidence map›Paper›PMID 26718502›Full record

ArticleDiabetes2016

An Essential Role of NRF2 in Diabetic Wound Healing.

Min Long, Montserrat Rojo de la Vega, Qing Wen, Manish Bharara, Tao Jiang, Rui Zhang, Shiwen Zhou, Pak K Wong, Georg T Wondrak, Hongting Zheng and 1 more

Abstract read
In one paragraph

Article in Diabetes, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
148citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

148 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Exploring the Role of GLP-1 Agents in Managing Diabetic Foot Ulcers: A Narrative and Systematic Review.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
    Pooled it
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88 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Min LongDepartment of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ Department of Endocrinology, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Montserrat Rojo de la VegaDepartment of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ.
Qing WenDepartment of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ Department of Pharmacy, Jinan Central Hospital, Shandong University, Shandong, People's Republic of China.
Manish BhararaSouthern Arizona Limb Salvage Alliance, Department of Surgery, The University of Arizona, Tucson, AZ.
Tao JiangDepartment of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ.
Rui ZhangDepartment of Endocrinology, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Shiwen ZhouBase for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Pak K WongDepartment of Biomedical Engineering, The Pennsylvania State University, University Park, PA.
Georg T WondrakDepartment of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ dzhang@pharmacy.arizona.edu fnf7703@hotmail.com wondrak@pharmacy.arizona.edu.
Hongting ZhengDepartment of Endocrinology, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China dzhang@pharmacy.arizona.edu fnf7703@hotmail.com wondrak@pharmacy.arizona.edu.
Donna D ZhangDepartment of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ dzhang@pharmacy.arizona.edu fnf7703@hotmail.com wondrak@pharmacy.arizona.edu.

Funding

VITAMIN AP30CA023074 · NCI · UNIVERSITY OF ARIZONA · PI Dan Theodorescu · 1985 to 2026
$110.2M
SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI DEAN BILLHEIMER · 1994 to 2026
$36.7M
The protective role of Nrf2 in arsenic-induced toxicity and carcinogenicityR01ES015010 · NIEHS · UNIVERSITY OF ARIZONA · PI ZHANG, DONNA D · 2006 to 2015
$3.4M
Investigation of an anti-cancer phytochemical targeting Nrf2R01CA154377 · NCI · UNIVERSITY OF ARIZONA · PI ZHANG, DONNA D · 2011 to 2015
$1.5M
Targeting colorectal carcinogenesis using a cinnamon-derived food factorR21CA166926 · NCI · UNIVERSITY OF ARIZONA · PI WONDRAK, GEORG T, ZHANG, DONNA D · 2013 to 2014
$358k
NCI NIH HHS P30 CA023074NCI NIH HHS R01 CA154377NCI NIH HHS R21 CA166926NCI NIH HHS R21CA166926NIEHS NIH HHS ES006694NIEHS NIH HHS P30 ES006694NIEHS NIH HHS R01 ES015010
6 · The paper itself

Abstract

The high mortality and disability of diabetic nonhealing skin ulcers create an urgent need for the development of more efficacious strategies targeting diabetic wound healing. In the current study, using human clinical specimens, we show that perilesional skin tissues from patients with diabetes are under more severe oxidative stress and display higher activation of the nuclear factor-E2-related factor 2 (NRF2)-mediated antioxidant response than perilesional skin tissues from normoglycemic patients. In a streptozotocin-induced diabetes mouse model, Nrf2(-/-) mice have delayed wound closure rates compared with Nrf2(+/+) mice, which is, at least partially, due to greater oxidative DNA damage, low transforming growth factor-β1 (TGF-β1) and high matrix metalloproteinase 9 (MMP9) expression, and increased apoptosis. More importantly, pharmacological activation of the NRF2 pathway significantly improves diabetic wound healing. In vitro experiments in human immortalized keratinocyte cells confirm that NRF2 contributes to wound healing by alleviating oxidative stress, increasing proliferation and migration, decreasing apoptosis, and increasing the expression of TGF-β1 and lowering MMP9 under high-glucose conditions. This study indicates an essential role for NRF2 in diabetic wound healing and the therapeutic benefits of activating NRF2 in this disease, laying the foundation for future clinical trials using NRF2 activators in treating diabetic skin ulcers.

Indexed as

AgedAnimalsApoptosisCase-Control StudiesCell ProliferationDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2Diabetic FootFemaleHumansImmunoblottingImmunohistochemistryKeratinocytesMaleMatrix Metalloproteinase 9Matrix Metalloproteinase 9NFE2L2 protein, humanNfe2l2 protein, mouseNF-E2-Related Factor 2Reactive Oxygen SpeciesTransforming Growth Factor beta1

Identifiers

PMID26718502
PMCPMC4764153

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.