Analysis of the proteomic profile of chronic pressure ulcers

Abstract

Analysis of the proteomic profile of pressure ulcers over time is a critical step in the identification of biomarkers of healing or nonhealing in pressure ulcers. The wound fluid from 32 subjects with 42 pressure ulcers was evaluated over 6 weeks at 15 time points. Samples specific to both the interior and the periphery of the wound bed were collected. Antibody screening arrays, isobaric tags for relative and absolute quantitation with mass spectrometry and multiplexed microarrays were used to characterize wound fluid and results were correlated with clinical outcome. Twenty-one proteins were found to distinguish between healed and chronic wounds and 19 proteins were differentially expressed between the interior and periphery of wounds. Four proteins, pyruvate kinase isozymes M1/M2, profilin-1, Ig lambda-1 chain C regions, and Ig gamma-1 chain C region, were present in lower levels for periphery samples when compared to interior samples and six proteins, keratin, type II cytoskeletal 6A (KRT6A), keratin, type I cytoskeletal 14, S100 calcium binding proteins A7, alpha-1-antitrypsin precursor, hemoglobin subunit alpha, and hemoglobin subunit beta, were present in higher levels in periphery samples when compared with interior samples. S100 calcium binding protein A6, S100 calcium binding protein A7, and soluble receptor for advanced glycation end-products had higher levels in the periphery of chronic wounds vs. the interior in planar arrays. A significant temporal trend was noted for monokine induced by gamma interferon (MIG), synonomous with chemokine (C-X-C motif) ligand 9 (CXCL9), which increased as wounds healed and remained nearly constant for ulcers that were not approaching closure.

Syndesome Therapeutics for Enhancing Diabetic Wound Healing

“…A proteomic analysis of chronic pressure ulcers in human patients found that MIG increases in chronic ulcers that heal but remains constant in those that do not heal. [24] …”

Wound repair and regeneration: Mechanisms, signaling, and translation

“…In pressure ulcers, chemokine (C-X-C motif) ligand 9 expression levels fail to increase as they do in healthy, healing wounds (51), leading to inhibition of endothelial cell chemotaxis at the proliferative stage of angiogenesis and subsequently aberrant angiogenesis (52). An ability to modulate the fine balance between pro- and antiangiogenic molecules might lead to novel therapeutics for induction of angiogenesis in a chronic wound.…”

Biology and Biomarkers for Wound Healing

“…Perpetuating this inflammatory state is polymicrobial infection of the wound; often with microbes capable of forming biofilms that together sustain the influx of proinflammatory cells while respectively hampering the “host response” to infection 17,19–22 . Impaired angiogenesis and vasculogenesis, through aberrant regulation and cleavage of growth factors, and their receptors leads to insufficient oxygenation and inadequate delivery of nutrients to the wound 23,24 . Epidermal stem cell dysfunction due to constant cycling and subsequent depletion together with deregulated chemokines necessary to recruit bone marrow and endothelial progenitors leads to inadequate healing 11,25 .…”