Effect of BTXA on Inhibiting Hypertrophic Scar Formation in a Rabbit Ear Model

Liu, Dongqing; Li, Xiaojing; Weng, Xiaojuan

doi:10.1007/s00266-017-0803-5

Cited by 24 publications

(10 citation statements)

References 24 publications

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“…The findings of this meta-analysis are supported by the findings from previous studies and reviews of the literature. Liu et al [36] and Fanous et al [37], showed botulinum toxin type A inhibited hypertrophic scars and keloids in animal models. A literature review published by Austin et al [38] also showed that botulinum toxin type A had the potential to prevent pathological scar formation in patients with a known individual history or family history of this condition.…”

Section: Discussionmentioning

confidence: 99%

Intralesional Injection of Botulinum Toxin Type A Compared with Intralesional Injection of Corticosteroid for the Treatment of Hypertrophic Scar and Keloid: A Systematic Review and Meta-Analysis

Sun

et al. 2019

Med Sci Monit

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Background The optimal treatment for hypertrophic scar and keloid remains controversial. Therefore, the aim of this systematic review and meta-analysis was to compare the effectiveness of intralesional injection of botulinum toxin type A compared with placebo and intralesional injection of corticosteroid compared with placebo in patients with hypertrophic scar and keloid. Material/Methods Six databases were searched using Medical Subject Headings (MeSH) keywords and included Web of Science, PubMed, EMBASE, the Cochrane Library, WanFang, and CNKI from their inception to March 1 2019, without language restriction. Randomized controlled trials (RCTs) and prospective controlled trials (PCTs) were identified that compared intralesional injection of botulinum toxin type A with placebo and corticosteroid with placebo in hypertrophic scar and keloid. The quality of controlled trials was assessed by the Newcastle-Ottawa Scale (NOS). Results Comparison of intralesional botulinum toxin type A and corticosteroid showed significant differences in the Visual Analog Scale (VAS) (P<0.001) (WMD, −4.30; 95% CI, −4.44 to −4.16) and effective rate (P=0.012) (RR=0.82; 95% CI, 0.70–0.96). Intralesional injection of botulinum toxin type A compared with placebo showed significant differences in the VAS (P<0.001) (WMD, 1.41; 95% CI, 1.21–1.62), the width of scar (P=0.00) (WMD, −0.15; 95% CI, −0.19 to −0.10) and Vancouver Scar Scale (VSS) (P=0.003) (WMD, −0.69; 95% CI, −1.14 to −0.23). Conclusions Systematic review and meta-analysis showed that injection of intralesional botulinum toxin type A was more effective in the treatment of hypertrophic scar and keloid than injection of intralesional corticosteroid or placebo.

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Section: Discussionmentioning

confidence: 99%

Intralesional Injection of Botulinum Toxin Type A Compared with Intralesional Injection of Corticosteroid for the Treatment of Hypertrophic Scar and Keloid: A Systematic Review and Meta-Analysis

Sun

et al. 2019

Med Sci Monit

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“…A hypertrophic scar is a clinically common skin fibroplasia disease that is caused by an excessive healing response of the human body to trauma (1). It is characterized by the abnormal proliferation of fibroblasts, abundant collagen synthesis and excessive collagen deposition (2). It was recently reported that the incidence of hypertrophic scars in burn patients in China reached 90% (3).…”

Section: Introductionmentioning

confidence: 99%

Decreased expression of microRNA‑145 promotes the biological functions of fibroblasts in hypertrophic scar tissues by upregulating the expression of transcription factor SOX‑9

Wang

et al. 2019

Exp Ther Med

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The present study aimed to determine the expression of microRNA (miRNA or miR)-145 in hypertrophic scars at the tissue and cellular levels, and to investigate its biological functions and mechanism of action. A total of 36 patients who were diagnosed with hypertrophic scar were included in the present study. Reverse transcription-quantitative polymerase chain reaction was used to determine the expression of miR-145 in tissues and fibroblasts. Primary fibroblasts were transfected with negative control miRNA, miR-145 mimics or inhibitor. A Cell Counting Kit-8 assay was performed to determine the level of proliferation of fibroblasts. Flow cytometry was employed for cell cycles determination and apoptosis in fibroblasts. A Matrigel assay was used to evaluate the invasion ability of fibroblasts. Western blotting was used to determine the expression of the transcription factor SOX-9 (SOX-9) protein in fibroblasts. Rescue experiments were performed to examine the effect of SOX-9 on the regulation of fibroblasts by miR-145. The dual luciferase reporter assay was performed to identify the direct interaction between SOX-9 and miR-145. The expression of miR-145 was reduced in hypertrophic tissues and fibroblasts. Overexpression of miR-145 inhibited the proliferation, G1/S phase transition and invasion of fibroblasts, and promoted the apoptosis of fibroblasts. In addition, overexpression of miR-145 inhibited SOX-9 protein expression. By contrast, the expression of SOX-9 reversed the effects of miR-145 on the proliferation, cell cycle, apoptosis and invasion of fibroblasts. The miR-145 seed region was able to bind with the 3′-untranslated region of the SOX-9 mRNA to regulate its expression. The present study demonstrated that miR-145 expression is reduced in hypertrophic scar tissues and negatively associated with SOX-9 expression. In addition, miR-145 inhibits the proliferation, cell cycle and invasion, and promotes the apoptosis of fibroblasts by down-regulating the expression of SOX-9. The current study provides a potential target for the clinical diagnosis and treatment of hypertrophic scars.

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“…The major effects of BTX include inhibition of muscle contraction and chronic inflammatory stimuli, which consequently reduces scar formation [6][7][8]28]. Moreover, a recent study showed that BTX injections inhibited the formation of HSs and collagen fibrils in a rabbit ear model [20].…”

mentioning

confidence: 99%

Botulinum toxin type A suppresses pro-fibrotic effects via the JNK signaling pathway in hypertrophic scar fibroblasts

Park

Yoon

et al. 2019

Arch Dermatol Res

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Hypertrophic scar is a dermal fibroproliferative disease characterized by the overproduction and deposition of extracellular matrix, and the hyperproliferation and enhanced angiogenesis of fibroblasts, along with their enhanced differentiation to myofibroblasts. Botulinum toxin type A shows potential for prevention of hypertrophic scar formation; however, its effectiveness in attenuating skin fibrosis and the related mechanism are unclear. In this study, human scar fibroblasts were cultured and stimulated with botulinum toxin type A, and the changes in fibroblast proliferation, migration, and protein expression of pro-fibrotic factors were evaluated with colorimetric, scratch, and enzyme-linked immunosorbent assays and western blotting, respectively. Botulinum toxin type A treatment decreased the proliferation and migration of human scar fibroblasts compared with those of untreated controls. Protein expression levels of pro-fibrotic factors (transforming growth factor β1, interleukin-6, and connective tissue growth factor) were also inhibited by botulinum toxin type A, whereas the JNK phosphorylation level was increased. Activation of the JNK pathway demonstrated the inhibitory effects of the toxin on human scar fibroblast proliferation and production of pro-fibrotic factors, suggesting that the suppressive effects of botulinum toxin type A are closely associated with JNK phosphorylation. Overall, this study showed that botulinum toxin type A has a suppressive effect on extracellular matrix production and scar-related factors in human scar fibroblasts in vitro, and that regulation of JNK signaling plays an important role in this process. Our results provide a theoretical basis, at the cellular level, for the therapeutic use of botulinum toxin type A.

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Effect of BTXA on Inhibiting Hypertrophic Scar Formation in a Rabbit Ear Model

Cited by 24 publications

References 24 publications

Intralesional Injection of Botulinum Toxin Type A Compared with Intralesional Injection of Corticosteroid for the Treatment of Hypertrophic Scar and Keloid: A Systematic Review and Meta-Analysis

Intralesional Injection of Botulinum Toxin Type A Compared with Intralesional Injection of Corticosteroid for the Treatment of Hypertrophic Scar and Keloid: A Systematic Review and Meta-Analysis

Decreased expression of microRNA‑145 promotes the biological functions of fibroblasts in hypertrophic scar tissues by upregulating the expression of transcription factor SOX‑9

Botulinum toxin type A suppresses pro-fibrotic effects via the JNK signaling pathway in hypertrophic scar fibroblasts

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