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Modification of collagen by 3-deoxyglucosone alters wound healing through differential regulation of p38 MAP kinase
Journal article   Open access

Modification of collagen by 3-deoxyglucosone alters wound healing through differential regulation of p38 MAP kinase

Danielle T Loughlin and Carol M Artlett
PloS one, v 6(5), pp e18676-e18676
06 May 2011
DOI: https://doi.org/10.1371/journal.pone.0018676
PMID: 21573155
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1371/journal.pone.0018676View
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Abstract

Humans Middle Aged Caspase 3 - metabolism Child, Preschool Pseudopodia - drug effects Young Adult Deoxyglucose - analogs & derivatives Deoxyglucose - pharmacology Mitogen-Activated Protein Kinase 1 - genetics Caspase 3 - genetics Aged, 80 and over Adult p38 Mitogen-Activated Protein Kinases - metabolism Wound Healing - genetics Child Wound Healing - drug effects Mitogen-Activated Protein Kinase 3 - genetics Cells, Cultured p38 Mitogen-Activated Protein Kinases - genetics Reverse Transcriptase Polymerase Chain Reaction Blotting, Western Collagen - metabolism Mitogen-Activated Protein Kinase 3 - metabolism Pseudopodia - metabolism Adolescent Fluorescent Antibody Technique Aged Cell Proliferation - drug effects Mitogen-Activated Protein Kinase 1 - metabolism
Wound healing is a highly dynamic process that requires signaling from the extracellular matrix to the fibroblasts for migration and proliferation, and closure of the wound. This rate of wound closure is impaired in diabetes, which may be due to the increased levels of the precursor for advanced glycation end products, 3-deoxyglucosone (3DG). Previous studies suggest a differential role for p38 mitogen-activated kinase (MAPK) during wound healing; whereby, p38 MAPK acts as a growth kinase during normal wound healing, but acts as a stress kinase during diabetic wound repair. Therefore, we investigated the signaling cross-talk by which p38 MAPK mediates wound healing in fibroblasts cultured on native collagen and 3DG-collagen. Using human dermal fibroblasts cultured on 3DG-collagen as a model of diabetic wounds, we demonstrated that p38 MAPK can promote either cell growth or cell death, and this was dependent on the activation of AKT and ERK1/2. Wound closure on native collagen was dependent on p38 MAPK phosphorylation of AKT and ERK1/2. Furthermore, proliferation and collagen production in fibroblasts cultured on native collagen was dependent on p38 MAPK regulation of AKT and ERK1/2. In contrast, 3DG-collagen decreased fibroblast migration, proliferation, and collagen expression through ERK1/2 and AKT downregulation via p38 MAPK. Taken together, the present study shows that p38 MAPK is a key signaling molecule that plays a significantly opposite role during times of cellular growth and cellular stress, which may account for the differing rates of wound closure seen in diabetic populations.

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Web of Science research areas
Biochemistry & Molecular Biology
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