Epithelial-mesenchymal interactions in keloid pathogenesis modulate vascular endothelial growth factor expression and...

Area of Science:

• Cell Biology
• Dermatology
• Wound Healing Research

Background:

• Vascular endothelial growth factor (VEGF) is crucial for angiogenesis in wound healing.
• Epithelial-mesenchymal interactions are known regulators of gene expression during wound repair.

Purpose of the Study:

• To investigate the role of epithelial-mesenchymal interactions in modulating VEGF expression and angiogenesis.
• To explore the potential of targeting VEGF for keloid scar treatment.

Main Methods:

• Utilized a two-chamber co-culture model with normal and keloid keratinocytes and fibroblasts.
• Quantified VEGF expression using ELISA and cell lysates.
• Assessed the angiogenic potential of conditioned media on human umbilical vein endothelial cells.
• Performed immunostaining on keloid and normal skin tissue.
• Tested the effect of inhibitors (WP631, mitoxantrone, Rapamycin) on VEGF expression.

Main Results:

• Co-culture of keratinocytes and fibroblasts increased VEGF expression.
• Keloid keratinocyte and fibroblast co-cultures significantly enhanced endothelial cell proliferation and capillary-like structure formation.
• Keloid tissue exhibited higher VEGF localization and blood vessel density compared to normal skin.
• Inhibitors WP631, mitoxantrone, and Rapamycin dose-dependently downregulated secreted VEGF in keloid co-cultures.

Conclusions:

• Epithelial-mesenchymal interactions play a significant role in regulating VEGF expression and angiogenesis during wound healing.
• Epidermal VEGF likely exerts paracrine control over dermal fibroblasts.
• Targeting VEGF pathways with compounds like WP631, mitoxantrone, or Rapamycin shows therapeutic potential for keloid scar management.