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Impact of the Diabetic State on Wound Healing Dynamics and Expression of Soluble Cellular Mediators

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Regenerative Medicine: Laboratory to Clinic

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Abstract

Diabetes mellitus impacts virtually every organ system of the body due to the influence that altered glucose metabolism imparts on cellular physiology and because of the effect chronic hyperglycemia can have on protein glycosylation states. As a physiological process involving multiple cell types, biomolecules, and a requirement for cell activation and activity, wound healing processes from formation of a transitional extracellular matrix after tissue destruction to altered neutrophil activation to a reduction in effective mesenchymal cell function have all been shown to be impacted by diabetes. In this chapter, we will review numerous studies that have documented changes in different components of classic dermal wound healing due to chronic hyperglycemia producing an overall diminished capacity to heal tissues and to even lead to the formation of ulcerations. Lastly, we will briefly discuss recent findings from our own studies that suggest that the diabetic state may alter the ability of fibroblasts to respond to activation stimuli with the appropriate expression of pro-inflammatory mediators. This aberrant expression could ultimately lead to an over-recruitment of neutrophils and/or monocyte/macrophages leading to a failure to heal a wound.

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Abbreviations

bFGF:

Basic fibroblast growth factor

CCR:

CC chemokine receptor

CXCR:

CXC chemokine receptor

ECM:

Extracellular matrix

HIF-1α:

Hypoxia-inducible factor-1α

IL:

Interleukin

LPS:

Lipopolysaccharide

MCP-1:

Monocyte chemoattractant protein-1

MMP:

Matrix metalloproteinase

NO:

Nitric oxide

PDGF:

Platelet-derived growth factor

TGFβ:

Transforming growth factor-β

TIMP:

Tissue inhibitor of matrix metalloproteinase

TLR:

Toll-like receptor

TNFα:

Tumor necrosis factor-α

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Authors and Affiliations

  1. Department of Basic Pharmaceutical Sciences, School of Pharmacy, Husson University, Bangor, ME, 04401, USA

    Stephanie E. Grant Pharm.D & William J. Lindblad Ph.D.

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  1. Stephanie E. Grant Pharm.D
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  2. William J. Lindblad Ph.D.
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Correspondence to William J. Lindblad Ph.D. .

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  1. Stem Cell Biology Laboratory, National Institute of Immunology, New Delhi, India

    Asok Mukhopadhyay

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Grant, S.E., Lindblad, W.J. (2017). Impact of the Diabetic State on Wound Healing Dynamics and Expression of Soluble Cellular Mediators. In: Mukhopadhyay, A. (eds) Regenerative Medicine: Laboratory to Clinic. Springer, Singapore. https://doi.org/10.1007/978-981-10-3701-6_1

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