4.7 Article

Imaging Mass Spectrometry for Assessing Cutaneous Wound Healing: Analysis of Pressure Ulcers

Journal

JOURNAL OF PROTEOME RESEARCH
Volume 14, Issue 2, Pages 986-996

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/pr5010218

Keywords

Pressure ulcers; imaging mass spectrometry; S-100 proteins; chronic wounds; proteomics; human defensin 6; calgranulin A; calgranulin B; calgizzarin; calcyclin

Funding

  1. Commission European Union
  2. European Social Funds (POR Calabria FSE)
  3. Region of Calabria (Taverna)
  4. NIH/NIAMS [AR056138-01A2]
  5. NIH/NIGMS [5P41 GM 103391-03]

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Imaging mass spectrometry (IMS) was employed for the analysis of frozen skin biopsies to investigate the differences between stage IV pressure ulcers that remain stalled, stagnant, and unhealed versus those exhibiting clinical and histological signs of improvement. Our data reveal a rich diversity of proteins that are dynamically modulated, and we selectively highlight a family of calcium binding proteins (S-100 molecules) including calcyclin (S100-A6), calgranulins A (S100-A8) and B (S100-A9), and calgizzarin (S100-A11). IMS allowed us to target three discrete regions of interest: the wound bed, adjacent dermis, and hypertrophic epidermis. Plots derived using unsupervised principal component analysis of the global protein signatures within these three spatial niches indicate that these data from wound signatures have potential as a prognostic tool since they appear to delineate wounds that are favorably responding to therapeutic interventions versus those that remain stagnant or intractable in their healing status. Our discovery-based approach with IMS augments current knowledge of the molecular signatures within pressure ulcers while providing a rationale for a focused examination of the role of calcium modulators within the context of impaired wound healing.

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