Optimal Mechanical Stretch Promotes TSP-1 Expression Through Akt and GSK-3β/β-Catenin Signaling Pathways in Keloid...

Area of Science:

• Wound healing research
• Dermatology
• Biomedical engineering

Background:

• Keloid formation is influenced by mechanical stretch.
• Thrombospondin-1 (TSP-1) is a known tension-sensitive protein.
• The role of TSP-1 in mechanical stretch-induced keloid formation is not well understood.

Purpose of the Study:

• To investigate the relationship between mechanical stretch and TSP-1 expression in keloid fibroblasts.
• To elucidate the signaling pathways involved in stretch-induced keloid formation.
• To assess the potential of TSP-1 inhibition as a therapeutic strategy for keloids.

Main Methods:

• Developed a mechanical stretch device for homogeneous equibiaxial stretch (HES).
• Utilized Western blot, RT-PCR, and immunohistochemistry to analyze protein expression and localization.
• Performed cell function assays and TSP-1 knockdown experiments in keloid fibroblasts (Kfbs).

Main Results:

• Optimal HES (oHES) significantly increased vimentin, collagen I (Col I), and fibronectin expression in Kfbs.
• oHES promoted Kfb proliferation and migration.
• oHES upregulated TSP-1 expression in vitro and in vivo, suggesting its role in keloid pathogenesis.

Conclusions:

• oHES promotes keloid formation by upregulating Col I expression.
• TSP-1 mediates stretch-induced keloid formation through the Akt and GSK-3β/β-catenin signaling pathways.
• Targeting TSP-1 may offer a novel therapeutic approach for managing keloids.