Targeting TEAD would be a potential strategy for scarless wound repair: A preliminary study

Acta Histochem. 2024 Dec 11;127(1):152223. doi: 10.1016/j.acthis.2024.152223. Online ahead of print.

Abstract

Despite of decades of efforts, novel approaches are still limited to attenuate or prevent skin scarring. A previous report published in Science demonstrated that inhibition of YAP promotes scarless wound repair by regeneration. Due to the difficult drugability of targeting YAP, we speculated that inhibition of TEAD, a partner molecule of YAP, might exist similar therapeutic potential. Therefore, the aim of the study was to evaluate therapeutical effect of a novel inhibitor of TEAD auto-palmitoylation, VT107, on scar formation in a cutaneous wound healing model. Our findings confirmed VT107 exhibited favorable effect on preventing scarring, manifesting as reducing fibroblast proliferation and collagen denaturation, decreasing TGF-β1 and collagen deposition, as well as connective tissue growth factor (CTGF) expression. These findings provide a novel insight for the development of anti-scarring strategies. TEAD would become an ideal target for the treatment of scars.

Keywords: Collagen; Cutaneous wound healing; Scarring; TEAD; YAP signaling.