Gallic acid inhibits fibroblast growth and migration in keloids through the AKT/ERK signaling pathway

Abstract

Keloids are a fibroproliferative disorder of the skin resulted from abnormal healing of injured or irritated skin and are characterized by the ability to spread beyond the original boundary of the wound. Here, we tested the effect of gallic acid (GA), a plant polyphenol with selective growth inhibitory effects in cancer, on the proliferation and invasion of keloid fibroblasts (KFs) isolated from patients undergoing surgery. GA inhibited KF proliferation, migration, and invasion in parallel with the downregulation of matrix metalloproteinase-1 and -3 and upregulation of tissue inhibitors of metalloproteinase-1. Flow cytometric analysis showed that GA inhibited cell cycle progression and induced apoptosis. The effects of GA on KFs occurred in parallel with the inhibition of AKT and ERK1/2, suggesting that GA acts by suppressing the AKT/ERK signaling pathway. In ex vivo explant cultures of keloid tissues, GA inhibited the migration of KFs to the wound area and suppressed the expression of angiogenic markers concomitant with the inhibition of collagen deposition. These results identify GA as a potential therapeutic agent for the treatment of keloids and suggest a potential mechanism underlying its protective effect.

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