Mast Cells Regulate Wound Healing in Diabetes.

Area of Science:

• Dermatology
• Immunology
• Endocrinology

Background:

• Diabetic foot ulceration is a severe complication of diabetes with limited treatment options.
• The role of mast cells (MCs) in diabetes-related skin complications and wound healing is not well understood.
• Mast cells are known to contribute to wound healing processes.

Purpose of the Study:

• To investigate the role of mast cells and their degranulation in diabetic wound healing.
• To explore the potential of modulating mast cell activity for therapeutic benefit in diabetic wound healing.

Main Methods:

• Examined mast cell degranulation in diabetic and non-diabetic human and mouse skin.
• Utilized mast cell-deficient mice and wild-type controls in wound healing models.
• Assessed the effects of mast cell degranulation inhibitors (disodium cromoglycate) and mast cell mediators (substance P) on wound healing.
• Measured vascular endothelial growth factor (VEGF) levels in diabetic and non-diabetic skin and mast cells.

Main Results:

• Increased degranulated MCs were observed in unwounded skin of diabetic patients and mice.
• Diabetes impaired post-wounding MC degranulation.
• Inhibiting MC degranulation improved wound healing in diabetic mice and shifted macrophages to the M2 phenotype.
• MC-deficient mice exhibited delayed wound healing, indicating a need for MC mediators.
• VEGF levels were reduced in diabetic mouse skin, and its release from human MCs decreased under hyperglycemia.
• Topical substance P improved wound healing in wild-type but not MC-deficient mice.

Conclusions:

• Non-degranulated mast cells in unwounded skin are necessary for effective wound healing.
• Therapies that inhibit mast cell degranulation show promise for improving wound healing in diabetes.
• Mast cell mediators, such as VEGF, play a critical role in diabetic wound repair.