Evidence map›Paper›PMID 25283348›Full record

ArticleMicrovascular research2015

Hyperglycemia and redox status regulate RUNX2 DNA-binding and an angiogenic phenotype in endothelial cells.

Maria T Mochin, Karen F Underwood, Brandon Cooper, John C McLenithan, Adam D Pierce, Cesar Nalvarte, Jack Arbiser, Anna I Karlsson, Alexander R Moise, Jackob Moskovitz and 1 more

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

Article in Microvascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

15 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. RUNX2 and Cancer.International journal of molecular sciences · 2023
    Review
  6. Matrigel: history/background, uses, and future applications.Journal of cell communication and signaling · 2022
    Article
  7. Bioenergetic Metabolism In Osteoblast Differentiation.Current osteoporosis reports · 2022
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
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

11 authors at 4 institutions in 1 country.

Maria T MochinDepartment of Pathology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Biochemistry & Molecular Biology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Medicine, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Marlene & Stewart Greenebaum Cancer Center, The University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Karen F UnderwoodDepartment of Pathology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Biochemistry & Molecular Biology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Medicine, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Marlene & Stewart Greenebaum Cancer Center, The University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Brandon CooperDepartment of Pathology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Biochemistry & Molecular Biology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Medicine, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Marlene & Stewart Greenebaum Cancer Center, The University of Maryland School of Medicine, Baltimore, MD 21201, USA.
John C McLenithanDepartment of Pathology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Biochemistry & Molecular Biology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Medicine, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Marlene & Stewart Greenebaum Cancer Center, The University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Adam D PierceDepartment of Pathology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Biochemistry & Molecular Biology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Medicine, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Marlene & Stewart Greenebaum Cancer Center, The University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Cesar NalvarteDepartment of Pathology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Biochemistry & Molecular Biology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Medicine, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Marlene & Stewart Greenebaum Cancer Center, The University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Jack ArbiserDepartment of Dermatology, Emory University, Atlanta, GA, USA; Atlanta Veterans Administration Medical Center, Atlanta, GA, USA.
Anna I KarlssonDepartment of Dermatology, Emory University, Atlanta, GA, USA; Atlanta Veterans Administration Medical Center, Atlanta, GA, USA.
Alexander R MoiseDepartment of Pharmacology and Toxicology, University of Kansas, Lawrence, KS 66045, USA.
Jackob MoskovitzDepartment of Pharmacology and Toxicology, University of Kansas, Lawrence, KS 66045, USA.
Antonino PassanitiDepartment of Pathology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Biochemistry & Molecular Biology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Medicine, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; Marlene & Stewart Greenebaum Cancer Center, The University of Maryland School of Medicine, Baltimore, MD 21201, USA; The Veteran's Health Administration Research & Development Service, Baltimore, MD, USA. Electronic address: apass001@umaryland.edu.
University of Maryland, Baltimore · USEmory University · USUniversity of Kansas · USUniversity of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center

Funding

Research BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D · 2005 to 2019
$17.3M
Cutaneous Hemangiomas and Signal TransductionR01AR047901 · NIAMS · EMORY UNIVERSITY · PI ARBISER, JACK L · 2001 to 2018
$4.3M
Novel Transcriptional Regulators of AngiogenesisR01CA108846 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI PASSANITI, ANTONINO · 2006 to 2009
$1.0M
Transcriptional regulation of tumor growthI01BX002205 · VA · BALTIMORE VA MEDICAL CENTER · PI PASSANITI, ANTONINO · 2014 to 2017
–
BLRD VA I01 BX002205NCI NIH HHS R01 CA108846NIAMS NIH HHS R01 AR047901NIDDK NIH HHS P30 DK072488
6 · The paper itself

Abstract

Angiogenesis is regulated by hyperglycemic conditions, which can induce cellular stress responses, reactive oxygen species (ROS), and anti-oxidant defenses that modulate intracellular signaling to prevent oxidative damage. The RUNX2 DNA-binding transcription factor is activated by a glucose-mediated intracellular pathway, plays an important role in endothelial cell (EC) function and angiogenesis, and is a target of oxidative stress. RUNX2 DNA-binding and EC differentiation in response to glucose were conserved in ECs from different tissues and inhibited by hyperglycemia, which stimulated ROS production through the aldose reductase glucose-utilization pathway. Furthermore, the redox status of cysteine and methionine residues regulated RUNX2 DNA-binding and reversal of oxidative inhibition was consistent with an endogenous Methionine sulfoxide reductase-A (MsrA) activity. Low molecular weight MsrA substrates and sulfoxide scavengers were potent inhibitors of RUNX2 DNA binding in the absence of oxidative stress, but acted as antioxidants to increase DNA binding in the presence of oxidants. MsrA was associated with RUNX2:DNA complexes, as measured by a sensitive, quantitative DNA-binding ELISA. The related RUNX2 protein family member, RUNX1, which contains an identical DNA-binding domain, was a catalytic substrate of recombinant MsrA. These findings define novel redox pathways involving aldose reductase and MsrA that regulate RUNX2 transcription factor activity and biological function in ECs. Targeting of these pathways could result in more effective strategies to alleviate the vascular dysfunction associated with diabetes or cancer.

Indexed as

Neovascularization, PathologicAldehyde ReductaseAngiogenesis InhibitorsAntioxidantsBinding SitesCells, CulturedCore Binding Factor Alpha 1 SubunitCore Binding Factor Alpha 2 SubunitDNADose-Response Relationship, DrugEndothelial CellsGlucoseHumansHuman Umbilical Vein Endothelial CellsHyperglycemiaMethionine Sulfoxide ReductasesAldehyde ReductaseAngiogenesis InhibitorsAntioxidantsCore Binding Factor Alpha 1 SubunitCore Binding Factor Alpha 2 SubunitDNAGlucosemethionine sulfoxide reductaseMethionine Sulfoxide ReductasesOxidantsRUNX1 protein, humanRUNX2 protein, humanAngiogenesisAntioxidant enzymesEndothelial cell differentiationOxidative stressTranscriptional factors

Identifiers

PMID25283348
PMCPMC4412363
OpenAlexW2051882822

What OpenQuestion holds

Textmetadata
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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.