Evidence map›Paper›PMID 32948607›Full record

ArticleDiabetes2020

Autophagy Inhibition Enables Nrf2 to Exaggerate the Progression of Diabetic Cardiomyopathy in Mice.

Huimei Zang, Weiwei Wu, Lei Qi, Wenbin Tan, Prakash Nagarkatti, Mitzi Nagarkatti, Xuejun Wang, Taixing Cui

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

Article in Diabetes, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 2 pooled it
10.9field-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

82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 112 citations in OpenAlex.

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22 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 2 institutions in 1 country.

Huimei ZangDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC.
Weiwei WuDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC.
Lei QiDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC.
Wenbin TanDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC.
Prakash NagarkattiDepartment of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC.
Mitzi NagarkattiDepartment of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC.
Xuejun WangDivision of Basic Biomedical Sciences, University of South Dakota Sanford School of Medicine, Vermillion, SD.
Taixing CuiDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC taixing.cui@uscmed.sc.edu.ORCID 0000-0002-9528-7299
University of South Carolina · USUniversity of South Dakota · US

Funding

Use of Resveratrol to treat experimental multiple sclerosisP01AT003961 · NCCIH · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, PRAKASH S · 2007 to 2018
$14.2M
Vascular Pathogenesis of Port Wine StainR01AR073172 · NIAMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI TAN, WENBIN · 2018 to 2022
$1.5M
The NRF2-p62 Axis in the Cross-Talk between Proteasomal and Lysosomal DegradationR01HL131667 · NHLBI · UNIVERSITY OF SOUTH DAKOTA · PI CUI, TAIXING, WANG, XUEJUN · 2017 to 2020
$1.4M
NCCIH NIH HHS P01 AT003961NHLBI NIH HHS R01 HL131667NIAMS NIH HHS R01 AR073172
6 · The paper itself

Abstract

Nuclear factor-erythroid factor 2-related factor 2 (Nrf2) may either ameliorate or worsen diabetic cardiomyopathy. However, the underlying mechanisms are poorly understood. Herein we report a novel mechanism of Nrf2-mediated myocardial damage in type 1 diabetes (T1D). Global Nrf2 knockout (Nrf2KO) hardly affected the onset of cardiac dysfunction induced by T1D but slowed down its progression in mice independent of sex. In addition, Nrf2KO inhibited cardiac pathological remodeling, apoptosis, and oxidative stress associated with both onset and advancement of cardiac dysfunction in T1D. Such Nrf2-mediated progression of diabetic cardiomyopathy was confirmed by a cardiomyocyte-restricted (CR) Nrf2 transgenic approach in mice. Moreover, cardiac autophagy inhibition via CR knockout of autophagy-related 5 gene (CR-Atg5KO) led to early onset and accelerated development of cardiomyopathy in T1D, and CR-Atg5KO-induced adverse phenotypes were rescued by additional Nrf2KO. Mechanistically, chronic T1D leads to glucolipotoxicity inhibiting autolysosome efflux, which in turn intensifies Nrf2-driven transcription to fuel lipid peroxidation while inactivating Nrf2-mediated antioxidant defense and impairing Nrf2-coordinated iron metabolism, thereby leading to ferroptosis in cardiomyocytes. These results demonstrate that diabetes over time causes autophagy deficiency, which turns off Nrf2-mediated defense while switching on an Nrf2-operated pathological program toward ferroptosis in cardiomyocytes, thereby worsening the progression of diabetic cardiomyopathy.

Indexed as

AnimalsAutophagyCell LineDiabetic CardiomyopathiesMiceMice, KnockoutMyoblastsNF-E2-Related Factor 2RatsNfe2l2 protein, mouseNF-E2-Related Factor 2

Identifiers

PMID32948607
PMCPMC7679777
OpenAlexW3087241439

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.