Evidence map›Paper›PMID 23597145›Full record

ArticleStem cell research & therapy2013

Oxidative stress-induced Notch1 signaling promotes cardiogenic gene expression in mesenchymal stem cells.

Archana V Boopathy, Karl D Pendergrass, Pao Lin Che, Young-Sup Yoon, Michael E Davis

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

46 citing papers in PubMed, 78 citations in OpenAlex.

  1. Review
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  9. Neurogenesis decreases in the offspring of mothers infected with influenza A virus.Frontiers in cellular and infection microbiology · 2025
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  14. Signaling pathways and targeted therapy for myocardial infarction.Signal transduction and targeted therapy · 2022
    Review
  15. Article
  16. Epigenetic Alterations under Oxidative Stress in Stem Cells.Oxidative medicine and cellular longevity · 2022
    Review
  17. Article
  18. A Novel PAK1-Notch1 Axis Regulates Crypt Homeostasis in Intestinal Inflammation.Cellular and molecular gastroenterology and hepatology · 2021
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Archana V Boopathy
Karl D Pendergrass
Pao Lin Che
Young-Sup Yoon
Michael E Davis
Parker Hannifin (United States) · USGeorgia Institute of Technology · US

Funding

Catalase therapy for cardiac regenerationR01HL094527 · NHLBI · EMORY UNIVERSITY · PI DAVIS, MICHAEL E · 2010 to 2013
$1.5M
NHLBI NIH HHS HL094527NHLBI NIH HHS R01 HL094527
6 · The paper itself

Abstract

introductionAdministration of bone marrow-derived mesenchymal stem cells (MSCs) after myocardial infarction (MI) results in modest functional improvements. However; the effect of microenvironment changes after MI, such as elevated levels of oxidative stress on cardiogenic gene expression of MSCs, remains unclear.

methodsMSCs were isolated from the bone marrow of adult rats and treated for 1 week with H2O2 (0.1 to 100 μM) or 48 hours with glucose oxidase (GOX; 0 to 5 mU/ml) to mimic long-term pulsed or short-term continuous levels of H2O2, respectively.

resultsIn 100 μM H2O2 or 5 mU/ml GOX-treated MSCs, mRNA expression of selected endothelial genes (Flt1, vWF, PECAM1), and early cardiac marker (nkx2-5, αMHC) increased significantly, whereas early smooth muscle markers (smooth muscle α-actin and sm22α) and fibroblast marker vimentin decreased, as measured with real-time PCR. Interestingly, mRNA expression and activity of the cell-surface receptor Notch1 were significantly increased, as were its downstream targets, Hes5 and Hey1. Co-treatment of MSCs with 100 μM H2O2 and a γ-secretase inhibitor that prevents Notch signaling abrogated the increase in cardiac and endothelial genes, while augmenting the decrease in smooth muscle markers. Further, on GOX treatment, a significant increase in Wnt11, a downstream target of Notch1, was observed. Similar results were obtained with adult rat cardiac-derived progenitor cells.

conclusionsThese data suggest that H2O2- or GOX-mediated oxidative stress upregulates Notch1 signaling, which promotes cardiogenic gene expression in adult stem/progenitor cells, possibly involving Wnt11. Modulating the balance between Notch activation and H2O2-mediated oxidative stress may lead to improved adult stem cell-based therapies for cardiac repair and regeneration.

Indexed as

Oxidative StressActinsAnimalsBone Marrow CellsCell DifferentiationCells, CulturedDipeptidesGene ExpressionGlucose OxidaseHydrogen PeroxideMaleMesenchymal Stem CellsMyocardiumRatsRats, Sprague-DawleyReceptor, Notch1ActinsDipeptidesGlucose OxidaseHydrogen PeroxideN-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl esterReceptor, Notch1RNA, Small InterferingWnt11 protein, ratWnt Proteins

Identifiers

PMID23597145
PMCPMC3706823
OpenAlexW2141312114

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.