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Neuropeptides, Inflammation, and Diabetic Wound Healing: Lessons from Experimental Models and Human Subjects

  • Ana Tellechea
  • Leena Pradhan-Nabzdyk
  • Frank W. LoGerfo
  • Aristidis Veves
Chapter
Part of the Contemporary Diabetes book series (CDI)

Abstract

Diabetic peripheral neuropathy and vascular disease, along with trauma, have long been recognized as major risk factors for the development of diabetic foot ulcerations (DFUs). More recently, chronic inflammation, abnormal extracellular matrix (ECM) remodeling, and reduced wound neovascularization, as a result of dysregulated cell function with imbalanced secretion of cytokines, matrix metalloproteinases, and growth factors, have been implicated in DFU failure to heal. Therefore, researchers are now focusing their efforts on further understanding the cellular and molecular mechanisms of diabetes-associated impaired wound healing, in an attempt to identify new targets and novel potential therapeutic approaches for DFUs, which remain a serious unmet clinical need. A growing body of evidence suggests an important role of neuropeptides in skin repair, particularly in diabetes, where neuropeptide levels are diminished. On the other hand, there is emerging interest in dissecting the mechanisms of dysregulated inflammation, namely the changes in immune cells, such as macrophages and mast cells (MCs), in diabetic wound healing. Studies using in vitro and in vivo models of diabetic wound healing have considerably improved our understanding of the healing process. However, the currently available models have major caveats and are not ideal to study chronic, complicated, and multifactorial wounds, such as DFUs. In this chapter we summarize the involvement of neuropeptides and mast cells in diabetic wound healing, highlighting the most recent findings. We also discuss the benefits and limitations of the current wound healing models, emphasizing the need for confirmation and/or validation in multiple models and/or tissue specimens from human subjects.

Keywords

Neuropeptides Mast cells Diabetic wound healing Substance P Neurotensin Pro-inflammatory Vascular permeability Calcitonin gene-related peptide Alpha-Melanocyte-stimulating hormone Inflammation In vivo models 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Ana Tellechea
    • 1
    • 2
  • Leena Pradhan-Nabzdyk
    • 3
  • Frank W. LoGerfo
    • 3
  • Aristidis Veves
    • 4
  1. 1.Beth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA
  2. 2.Division of Translational Medicine, Department of MedicineNew York University School of MedicineNew YorkUSA
  3. 3.Division of Vascular and Endovascular Surgery, Department of SurgeryBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA
  4. 4.The Rongxiang Xu, MD, Center for Regenerative Therapeutics Research Director, Joslin-Beth Israel Deaconess Foot CenterBeth Israel Deaconess Medical CenterBostonUSA

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