Impaired Wound Healing in Diabetic Ulcers: Accelerated Healing Through Depletion of Ganglioside

Duncan Hieu M. Dam*, Sophia A. Jelsma, Amy Paller

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

Cutaneous wound healing requires an organized series of complicated biological and molecular processes that depends on normal cellular responses to cytokines, growth factors, and other mediators such as clotting factors, prostaglandins, free radicals, and nitric oxide. In diabetic ulcers, the responses to these molecules are impaired, leading to abnormalities in vascularization, innervation, matrix reconstruction, and cell migration and proliferation. Re-epithelialization of wounds, which requires keratinocyte migration and proliferation on an extracellular matrix in response to growth factors, is slowed by inhibition of the insulin/IGF-1 signaling axis in diabetes. Ganglioside GM3, a sialylated epidermal glycosphingolipids, has been identified as one of the key factors in regulating this signaling pathway. Decreased expression of GM3 and the enzyme required for its synthesis, GM3 synthase (GM3S), increase insulin/IGF-1 receptor signaling, thereby enhancing keratinocyte migration. GM3 depletion, as in GM3S knock-out diet-induced diabetic mice and diet-induced diabetic mice treated topically with nanoconstruct-mediated GM3S-targeting gene regulation, accelerates wound healing. These findings suggest that GM3-depleting strategies are a promising new approach for human diabetic wounds.

Original languageEnglish (US)
Title of host publicationWound Healing
Subtitle of host publicationStem Cells Repair and Restorations, Basic and Clinical Aspects
EditorsK Turksen
Place of PublicationHoboken
PublisherWiley Blackwell
Pages167-175
Number of pages9
ISBN (Electronic)9781119282518
ISBN (Print)9781119282488
DOIs
StatePublished - Jan 23 2018

Keywords

  • Diabetic ulcers
  • Ganglioside
  • Ganglioside depletion
  • KC migration
  • Wound healing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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