Abnormally Elevated PKCδ Delays Diabetic Wound Healing by Inhibiting the GAD1-GABA Pathway

Area of Science:

• Endocrinology
• Molecular Biology
• Wound Healing Research

Background:

• Diabetic foot ulcers (DFU) are a severe diabetes complication with impaired healing.
• Protein kinase C delta (PKCδ) plays a role in DFU pathogenesis, but mechanisms are unclear.

Purpose of the Study:

• To investigate the role of PKCδ in DFU pathogenesis.
• To elucidate the molecular mechanisms underlying PKCδ's effect on endothelial cells and wound healing.

Main Methods:

• Human umbilical vein endothelial cells (HUVECs) were cultured in high glucose with PKCδ knockdown.
• Metabolomics identified key metabolites.
• GAD1 and GABA levels were modulated.
• In vivo studies used diabetic mice with topical GABA treatment.

Main Results:

• PKCδ knockdown increased GAD1 and GABA, enhancing HUVEC proliferation, migration, and tube formation while reducing apoptosis.
• GABA accelerated diabetic wound healing in mice, increasing angiogenesis and proliferation.
• Inhibition of GAD1 impaired endothelial cell function.

Conclusions:

• PKCδ inhibition of the GAD1-GABA pathway impairs endothelial cell function under high glucose, delaying diabetic wound healing.
• The GAD1-GABA pathway is crucial for endothelial cell function and diabetic wound repair.