Zhu Zhu; Jiqiong Wang; Yubo Wang; & Jiali Xu
Hypertrophic scars (HS) represent a challenging fibroproliferative disorder characterized by excessive fibroblast proliferation and collagen deposition following abnormal wound healing. This study investigates the regenerative potential of botulinum toxin (BTX) in inhibiting the c-Jun N-terminal kinase (JNK) signaling pathway, which plays a critical role in promoting pro-fibrotic effects in HS fibroblasts. Using both in vitro models and a rat HS model, we demonstrate that BTX significantly suppresses JNK phosphorylation, leading to reduced fibroblast proliferation (p < 0.05) and collagen synthesis (p < 0.05). Our results indicate that BTX disrupts the JNK/RAC1/ATF2 signaling axis, restoring the expression of JUN (p < 0.05), a transcription factor associated with fibroblast quiescence and apoptosis.Additionally, BTX enhances antioxidant capacity and reduces oxidative stress, reflected in increased thiol levels (p < 0.05) and decreased lipid peroxidation (TBARS: p < 0.05). Histological assessments reveal normalization of skin appendage densities and partial restoration of epidermal architecture following BTX treatment. However, persistent interstitial fibrosis underscores the need for combinatorial therapies that address both cellular signaling and the mechanical properties of the extracellular matrix. This research establishes BTX as a multifaceted therapeutic agent in scar management, effectively bridging neurogenic inflammation and JNK-mediated ECM dysregulation. The findings support the need for future clinical trials to evaluate staged regimens that integrate BTX with mechanotransduction-targeted adjuvants, aiming to optimize scar regression and enhance therapeutic outcomes for patients with hypertrophic scars.
KEY WORDS: Hypertrophic scars; JNK signaling pathway; Apoptosis; Skin; Inflammation.
ZHU, Z.; WANG, J.; WANG, Y. & XU, J. Regenerative potential of botulinum toxin in inhibiting JNK signaling pathway-mediated pro- fibrotic effects in hypertrophic scar fibroblasts. Int. J. Morphol., 44(4):1396-1405, 2026.
