Gangliosides in Diabetic Wound Healing

Duncan Hieu M. Dam, Amy S. Paller*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Scopus citations

Abstract

An organized series of complicated biological and molecular phenomena is required for normal skin wound healing. These processes depend on normal cellular responses to cytokines, growth factors, and other mediators, such as clotting factors, prostaglandins, free radicals, and nitric oxide. In diabetic ulcers, impaired responses to these molecules lead to abnormalities in vascularization, innervation, matrix reconstruction, and reepithelialization of wounds. keratinocyte migration and proliferation on an extracellular matrix is critical in reepithelialization, but the response to growth factors is blunted in diabetes, including the insulin/IGF-1signaling axis. Ganglioside GM3, a sialylated epidermal glycosphingolipid, has been identified as a key mediator of the inhibition of insulin/IGF-1 signaling in response to factors, such as tumor necrosis factor-alpha (TNF-α) and hyperglycemia. Decreased expression of GM3 and the enzyme required for its synthesis, GM3 synthase (GM3S), leads to increased insulin/IGF-1 receptor signaling and accelerated keratinocyte migration, even in the presence of high glucose levels. GM3 depletion in GM3S knockout diabetic mice and diet-induced diabetic mice treated topically with nanoconstruct-mediated GM3S-targeting gene regulation also accelerates wound healing. These recent observations, coupled with evidence that GM3 depletion reverses distal innervation abnormalities in diabetic mice, suggest that GM3-depleting strategies are a promising new approach for human diabetic wounds.

Original languageEnglish (US)
Title of host publicationProgress in Molecular Biology and Translational Science
EditorsRonald L. Schnaar, Pablo H.H. Lopez
PublisherElsevier B.V.
Pages229-239
Number of pages11
ISBN (Print)9780128123416
DOIs
StatePublished - Jan 1 2018

Publication series

NameProgress in Molecular Biology and Translational Science
Volume156
ISSN (Print)1877-1173
ISSN (Electronic)1878-0814

Keywords

  • diabetic ulcers
  • ganglioside
  • ganglioside depletion
  • keratinocyte migration
  • wound healing

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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