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

Background and Aims The formation of keloids is influenced by mechanical stretch. Thrombospondin‐1 (TSP‐1) is identified as a tension‐sensitive protein. However, the relationship between TSP‐1 and keloid formation induced by mechanical stretch remains unknown. Methods A simple customized mechanical stretch device was used for the application of homogeneous equibiaxial stretch (HES). Using Western blot and RT‐PCR, the optimal stretch strength and duration were determined. Regarding the functional changes induced by stretch in keloid fibroblasts (Kfbs), cell function assays were used. The relationship between TSP‐1 expression and stretch‐induced scar formation in human and animal models was investigated using immunohistochemistry. The knockdown of TSP‐1 in fibroblasts served as a reverse test. Results Optimal HES (oHES) could be achieved with four rotations of the screws on our mechanical stretch device, resulting in a significant increase in vimentin, Col I, and fibronectin expression in Kfbs on Day 5. Additionally, oHES significantly promoted cell proliferation and migration. oHES resulted in the upregulation of TSP‐1 expression in both in vitro and in vivo experimental settings. The inhibition of TSP‐1 may attenuate oHES‐induced keloid formation through the Akt and GSK‐3β/β‐catenin signaling pathways. Conclusion The results confirmed that oHES promoted keloid formation by increasing Col I expression through TSP‐1‐mediated Akt and GSK‐3β/β‐catenin signaling pathways.