The Effects and Mechanisms of Botulinum Toxin Type A on Hypertrophic Scars and Keloids.

[BACKGROUND] Keloids and hypertrophic scars are characterized by pathologically excessive dermal fibrosis and aberrant wound healing. These pathological scars are characterized by continuous and histologically localized inflammation of the reticular dermis. Although several treatments have been used for hypertrophic scar and keloid, there is still no consensus and for the majority of patients, management is driven by individual clinical experience. Injection of intralesional botulinum toxin type A (BTX) was more effective in the treatment of hypertrophic scar and keloid than injection of placebo. However, little is known about the mechanism of BTX in the treatment of hypertrophic scar and keloid.

[METHODS] We used mice wound healing model to track the response of fibrous repair. The histological changes of the fibrous repair were measured by H&E, Masson and immunohistochemical staining. The quantitative analysis macrophages and angiogenesis were measured by immunohistochemical staining. The expression of Th1- and Th2-associated cytokines was measured by qPCR. We also measured oxoglutarate dehydrogenase (OGDH) and pyruvate dehydrogenase (PDH) activity, OGDH positive cells and mRNA used enzyme activity assay kits, immunohistochemical staining and qPCR, respectively.

[RESULTS] We discovered that BTX injection disrupted wound healing and fibrous repair, and reduced M1 macrophages infiltration and M2 macrophages polarization, while increased total macrophages number. BTX injection reduced Il1b, Il6 and TNF-alpha mRNA level, and induced Il13 and Il4 mRNA level. BTX injection reduced OGDH activity.

[CONCLUSIONS] BTX alter the pattern of immunometabolism that change the phenotype of macrophages, which inhibits keloids and hypertrophic scars.

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