Evidence map›Paper›PMID 25437049›Full record

ArticleEpigenetics2014

Genome-wide DNA methylation analysis identifies a metabolic memory profile in patient-derived diabetic foot ulcer fibroblasts.

Lara K Park, Anna G Maione, Avi Smith, Behzad Gerami-Naini, Lakshmanan K Iyer, David J Mooney, Aristidis Veves, Jonathan A Garlick

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

Article in Epigenetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

45 citing papers in PubMed, 63 citations in OpenAlex.

  1. Trial
  2. Folinic Acid Improves Healing of Diabetic Foot Ulcers.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
    Trial
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Metabolic memory: mechanisms and diseases.Signal transduction and targeted therapy · 2024
    Review
  10. Fibroblasts in Diabetic Foot Ulcers.International journal of molecular sciences · 2024
    Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. Review
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 4 institutions in 2 countries.

Lara K Parka Department of Oral and Maxillofacial Pathology ; Oral Medicine and Craniofacial Pain ; Tufts University School of Dental Medicine ; Boston , MA USA.
Anna G Maione
Avi Smith
Behzad Gerami-Naini
Lakshmanan K Iyer
David J Mooney
Aristidis Veves
Jonathan A Garlick
Tufts University · USBeth Israel Deaconess Medical Center · USNational Medical Research Center of Dentistry and Maxillofacial Surgery · RUWyss Institute for Biologically Inspired Engineering

Funding

TUSM/T-NEMC CENTER FOR NEUROSCIENCE RESEARCH - Imaging CoreP30NS047243 · NINDS · TUFTS UNIVERSITY BOSTON · PI JACKSON, F ROB · 2003 to 2017
$10.0M
iPSC-derived Repair-Responsive Fibroblasts to Heal Diabetic Foot UlcersR01DK098055 · NIDDK · TUFTS UNIVERSITY BOSTON · PI GARLICK, JONATHAN A · 2012 to 2015
$2.6M
NIDDK NIH HHS R01 DK098055NINDS NIH HHS P30 NS047243
6 · The paper itself

Abstract

Diabetic foot ulcers (DFUs) are a serious complication of diabetes. Previous exposure to hyperglycemic conditions accelerates a decline in cellular function through metabolic memory despite normalization of glycemic control. Persistent, hyperglycemia-induced epigenetic patterns are considered a central mechanism that activates metabolic memory; however, this has not been investigated in patient-derived fibroblasts from DFUs. We generated a cohort of patient-derived lines from DFU fibroblasts (DFUF), and site- and age-matched diabetic foot fibroblasts (DFF) and non-diabetic foot fibroblasts (NFF) to investigate global and genome-wide DNA methylation patterns using liquid chromatography/mass spectrometry and the Illumina Infinium HumanMethylation450K array. DFFs and DFUFs demonstrated significantly lower global DNA methylation compared to NFFs (p = 0.03). Hierarchical clustering of differentially methylated probes (DMPs, p = 0.05) showed that DFFs and DFUFs cluster together and separately from NFFs. Twenty-five percent of the same probes were identified as DMPs when individually comparing DFF and DFUF to NFF. Functional annotation identified enrichment of DMPs associated with genes critical to wound repair, including angiogenesis (p = 0.07) and extracellular matrix assembly (p = 0.035). Identification of sustained DNA methylation patterns in patient-derived fibroblasts after prolonged passage in normoglycemic conditions demonstrates persistent metabolic memory. These findings suggest that epigenetic-related metabolic memory may also underlie differences in wound healing phenotypes and can potentially identify therapeutic targets.

Indexed as

DNA MethylationEpigenesis, GeneticAdultAgedCell LineComputational BiologyDiabetic FootFemaleFibroblastsHumansMaleMiddle AgedANOVA, Analysis of VarianceBMP, Bone Morphogenic ProteinCOL4A1, Collagen 4A1DAVID, Database for Annotation, Visualization, and Integrative DiscoveryDCCT, Diabetes Control and Complications TrialDFF, Diabetic Foot FibroblastDFU, Diabetic Foot UlcerDFUF, Diabetic Foot Ulcer FibroblastDHS, DNase Hypersensitive Sitediabetesdiabetic foot ulcerDMP, Differentially Methylated ProbeDNA methylationdNTPs, deoxynucleotideECM, Extracellular MatrixEDIC, Epidemiology of Diabetes Interventions and ComplicationsENCODE, Encyclopedia of DNA ElementsepigeneticsFGF1, Fibroblast Growth Factor 1fibroblastHbA1c, Hemoglobin A1cmetabolic memoryNFF, Non-diabetic Foot FibroblastNHLF, Normal Human Lung FibroblastPLAU, Plasminogen Activator UrokinaseSNP, Single Nucleotide PolymorphismTFBS, Transcription Factor Binding SiteTGFb, Transforming Growth Factor bTNFa, Tumor Necrosis Factor aTSS, Transcription Start SiteUTR, Untranslated Region.wound healing

Identifiers

PMID25437049
PMCPMC4622843
OpenAlexW2057558356

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.