Evidence map›Paper›PMID 30352880›Full record

ArticleDiabetes2019

Dysregulation of Nrf2/Keap1 Redox Pathway in Diabetes Affects Multipotency of Stromal Cells.

Piul S Rabbani, Marc A Soares, Sophia G Hameedi, Rohini L Kadle, Adnan Mubasher, Maria Kowzun, Daniel J Ceradini

Abstract read
In one paragraph

Article in Diabetes, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 5% 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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.

  1. Pooled it
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  7. Review
  8. Article
  9. Muscle-Derived miR-200a-3p Through Light-Intensity Exercise May Contribute to Improve Memory Dysfunction in Type 2 Diabetic Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  10. Article
  11. Article
  12. Diabetic neuropathy: A NRF2 disease?Journal of diabetes · 2024
    Review
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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

7 authors at 1 institution in 1 country.

Piul S RabbaniHansjörg Wyss Department of Plastic Surgery, New York University School of Medicine, New York, NY piul.rabbani@nyumc.org daniel.ceradini@nyumc.org.ORCID 0000-0001-8302-8225
Marc A SoaresHansjörg Wyss Department of Plastic Surgery, New York University School of Medicine, New York, NY.
Sophia G HameediHansjörg Wyss Department of Plastic Surgery, New York University School of Medicine, New York, NY.
Rohini L KadleHansjörg Wyss Department of Plastic Surgery, New York University School of Medicine, New York, NY.
Adnan MubasherHansjörg Wyss Department of Plastic Surgery, New York University School of Medicine, New York, NY.
Maria KowzunHansjörg Wyss Department of Plastic Surgery, New York University School of Medicine, New York, NY.
Daniel J CeradiniHansjörg Wyss Department of Plastic Surgery, New York University School of Medicine, New York, NY piul.rabbani@nyumc.org daniel.ceradini@nyumc.org.
New York University · US

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1M
Ventana Medical Systems Discovery XTS10OD010584 · OD · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CHIRIBOGA, LUIS A · 2013 to 2013
$127k
Sandy Recovery Ventana Medical Systems Discovery XTS10OD018338 · OD · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CHIRIBOGA, LUIS A · 2014 to 2014
$123k
NCI NIH HHS P30 CA016087NIH HHS S10 OD010584NIH HHS S10 OD018338
6 · The paper itself

Abstract

The molecular and cellular level reaches of the metabolic dysregulations that characterize diabetes are yet to be fully discovered. As mechanisms underlying management of reactive oxygen species (ROS) gain interest as crucial factors in cell integrity, questions arise about the role of redox cues in the regulation and maintenance of bone marrow-derived multipotent stromal cells (BMSCs) that contribute to wound healing, particularly in diabetes. Through comparison of BMSCs from wild-type and diabetic mice, with a known redox and metabolic disorder, we found that the cytoprotective nuclear factor erythroid-related factor 2 (Nrf2)/kelch-like erythroid cell-derived protein 1 (Keap1) pathway is dysregulated and functionally insufficient in diabetic BMSCs (dBMSCs). Nrf2 is basally active, but in chronic ROS, we found irregular inhibition of Nrf2 by Keap1, altered metabolism, and limited BMSC multipotency. Forced upregulation of Nrf2-directed transcription, through knockdown of Keap1, restores redox homeostasis. Normalized Nrf2/Keap1 signaling restores multipotent cell properties in dBMSCs through Sox2 expression. These restored BMSCs can resume their role in regenerative tissue repair and promote healing of diabetic wounds. Knowledge of diabetes and hyperglycemia-induced deficits in BMSC regulation, and strategies to reverse them, offers translational promise. Our study establishes Nrf2/Keap1 as a cytoprotective pathway, as well as a metabolic rheostat, that affects cell maintenance and differentiation switches in BMSCs.

Indexed as

AnimalsBlotting, WesternCell DifferentiationDiabetes Mellitus, ExperimentalEnzyme-Linked Immunosorbent AssayImmunohistochemistryImmunophenotypingKelch-Like ECH-Associated Protein 1MiceMice, Inbred C57BLNF-E2-Related Factor 2Oxidation-ReductionOxidative StressReactive Oxygen SpeciesReverse Transcriptase Polymerase Chain ReactionSignal TransductionKelch-Like ECH-Associated Protein 1NF-E2-Related Factor 2Reactive Oxygen SpeciesSox2 protein, mouseSOXB1 Transcription Factors

Identifiers

PMID30352880
PMCPMC6302538
OpenAlexW2898013597

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.