Botulinum toxin A promotes the transdifferentiation of primary keloid myofibroblasts into adipocyte-like cells

Keloid is a type of unusually raised scar. Botulinum toxin A (BTX-A) has a great application potential in keloids treatment. Here, we investigated the functional role of BTX-A in keloids. We separated keloid tissues and normal skin tissues from keloid patients and found that the expression of myofibroblast markers, alpha-SMA, Collagen I, and Collagen III was increased in the keloid tissues as compared with normal skin tissues. Keloid fibroblasts derived from keloid tissues were treated with TGF-beta 1 to induce the differentiation of fibroblasts into myofibroblasts. The keloid myofibroblasts displayed a significant up-regulation of alpha-SMA. BTX-A enhanced the expression of adipocyte markers, PPAR gamma and C/EBP alpha, and increased the accumulation of lipid droplets, and reduced the expression of alpha-SMA, Collagen I, and Collagen III in the keloid myofibroblasts. Moreover, BTX-A enhanced the expression of BMP4 and p-smad1/5/8. Noggin (BMP4 antagonist) treatment reversed BTX-A-mediated increase of PPAR gamma and C/EBP alpha expression and lipid droplets, and down-regulation of alpha-SMA, Collagen I, and Collagen III in primary keloid myofibroblasts. In conclusion, BTX-A promoted the transdifferentiation of primary keloid myofibroblasts into adipocyte-like cells, which may attribute to activate BMP4/Smad signalling pathway. Thus, this study provides new insights into the mechanism of BTX-A in keloid.