4.7 Review

Phosphatidylglycerol to Treat Chronic Skin Wounds in Diabetes

Journal

PHARMACEUTICS
Volume 15, Issue 5, Pages -

Publisher

MDPI
DOI: 10.3390/pharmaceutics15051497

Keywords

aquaporin-3 (AQP3); chronic wounds; diabetes; dioleoylphosphatidylglycerol (DOPG); inflammation; mitochondrial function; phosphatidylglycerol; phospholipase D2 (PLD2); wound healing

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This review suggests the use of DOPG as a potential treatment to improve healing of diabetic wounds. Diabetic wounds are characterized by enhanced inflammation and oxidative stress, which impair the ability of keratinocytes to restore epidermal integrity. DOPG, by promoting keratinocyte proliferation and inhibiting inflammation, shows promise in counteracting these detrimental effects and promoting wound healing.
This review proposes the use of dioleoylphosphatidylglycerol (DOPG) to enhance diabetic wound healing. Initially, the characteristics of diabetic wounds are examined, focusing on the epidermis. Hyperglycemia accompanying diabetes results in enhanced inflammation and oxidative stress in part through the generation of advanced glycation end-products (AGEs), in which glucose is conjugated to macromolecules. These AGEs activate inflammatory pathways; oxidative stress results from increased reactive oxygen species generation by mitochondria rendered dysfunctional by hyperglycemia. These factors work together to reduce the ability of keratinocytes to restore epidermal integrity, contributing to chronic diabetic wounds. DOPG has a pro-proliferative action on keratinocytes (through an unclear mechanism) and exerts an anti-inflammatory effect on keratinocytes and the innate immune system by inhibiting the activation of Toll-like receptors. DOPG has also been found to enhance macrophage mitochondrial function. Since these DOPG effects would be expected to counteract the increased oxidative stress (attributable in part to mitochondrial dysfunction), decreased keratinocyte proliferation, and enhanced inflammation that characterize chronic diabetic wounds, DOPG may be useful in stimulating wound healing. To date, efficacious therapies to promote the healing of chronic diabetic wounds are largely lacking; thus, DOPG may be added to the armamentarium of drugs to enhance diabetic wound healing.

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