Botulinum toxin type A attenuates hypertrophic scar formation via the inhibition of TGF‐β1/Smad and ERK pathways

Abstract Background Hypertrophic scar is a common complication in would healing process, and how to effectively prevent and treat it has been a hot and difficult research issue. Previous studies have showed that botulinum toxin type A (BTA) has effects on the prevention and treatment of hypertrophic scar, but little is known about the specific mechanisms. Objective This study aimed to explore the potential mechanisms of BTA on the inhibition of hypertrophic scar formation. Methods Hypertrophic scar‐derived human fibroblasts were cultured and then treated with transforming growth factor‐β1 (TGF‐β1) and various concentrations of BTA. Cell proliferation and viability were measured by CellTiter 96® AQueous One Solution Cell Proliferation Assay and trypan blue staining, respectively. The total amount of collagen was examined using Sirius red staining. Collagen I and Collagen III in the culture supernatant were evaluated by enzyme‐linked immunosorbent assay. Reverse transcription‐quantitative polymerase chain reaction and Western blot analysis were performed to detect the transcription and translation levels. Results Our results revealed that BTA decreased the proliferation of hypertrophic scar‐derived human fibroblasts. The mRNA and protein expression levels of alpha‐smooth muscle actin, collagen I, and collagen III induced by TGF‐β1 were inhibited by BTA in a dose‐dependent manner. BTA also inhibited the phosphorylation of Smad2/3 and ERK. Conclusion BTA decreased the proliferation of fibroblasts and prevented overdeposition of ECM through the inhibition of the TGF‐β1/Smad and ERK pathways. The findings of this study provide new scientific reference for the prevention and treatment of hypertrophic scar.