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

Dai, Xing; Lei, Tiechi

doi:10.1111/bcpt.13661

Cited by 11 publications

(8 citation statements)

References 23 publications

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“…Botulinum toxin type-A (Botox), well known for its muscle paralyzing activity for cosmetic concerns, appears to have an inhibitory effect on fibroblasts and collagen remodeling activity [ 11 , 12 ]. Its emerging off-label uses as intradermally injected micro-dosed Botox for aesthetic concerns, e.g., improving skin texture is an interesting area of research [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Microneedling combined with botulinum toxin-A versus microneedling combined with platelet-rich plasma in treatment of atrophic acne scars: a comparative split face study

et al. 2022

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Background Atrophic post-acne scarring constitutes a troublesome cosmetic concern for both patients and dermatologists. Old and new therapies as well as combinations are being introduced to achieve a satisfactory response. Microneedling has been used either alone or under different combinations for its treatment. The aim was to compare its combination with topical platelet-rich plasma versus its combination with topical Botulinum Toxin-A. Methods 30 subjects with different types and grades of atrophic post-acne scars completed the study. Right side of the face was treated with microneedling and platelet-rich plasma while the left side was treated microneedling and Botox. Response was assessed using two different scales. Patient satisfaction and pain were also assessed. Results Regarding response to therapy and according to the quartile grading scale, there was no statistically significant difference between the two sides where (23.4% & 13.3%) of the right and left sides, respectively, had an excellent response. Regarding the difference in the qualitative global scarring grading system before and after treatment, there was a highly statistically significant improvement on both sides with higher improvement on the right side than left side but in a non-statistically significant way. Conclusions Both combinations present efficacious options for treating acne scars with comparable efficacy. Trial registration Registered and approved prospectively by the ethical review board of the faculty of medicine, Zagazig University.

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Section: Introductionmentioning

confidence: 99%

Microneedling combined with botulinum toxin-A versus microneedling combined with platelet-rich plasma in treatment of atrophic acne scars: a comparative split face study

et al. 2022

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“…Overexpression of elastin in keloids was described by Russel et al 14 a long time ago in cultures of keloid fibroblasts. Hellstrom et al 15 reported a week distribution of collagen III in keloids, while more recently, Hsu et al 16 and Dai et al 17 described Very few data are available about keloid sublocations. The microarray analysis published by Seifert et al 13 about three keloids from various localization (chest, abdomen and upper back) showed a higher collagen I expression in the periphery than in the centre.…”

Section: Discussionmentioning

confidence: 99%

Evidence of inter‐ and intra‐keloid heterogeneity through analysis of dermal fibroblasts: A new insight in deciphering keloid physiopathology

Serror

Ferrero

Boismal

et al. 2023

Experimental Dermatology

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Keloid scars are hypertrophic and proliferating pathological scars extending beyond the initial lesion and without tendency to regression. Usually, keloids are considered and treated as a single entity but clinical observations suggest heterogeneity in keloid morphologies with distinction of superficial/extensive and nodular entities. Within a keloid, heterogeneity could also be detected between superficial and deep dermis or centre and periphery. Focusing on fibroblasts as main actors of keloid formation, we aimed at evaluating intra‐ and inter‐keloid fibroblast heterogeneity by analysing their gene expression and functional capacities (proliferation, migration, traction forces), in order to improve our understanding of keloid pathogenesis. Fibroblasts were obtained from centre, periphery, papillary and reticular dermis from extensive or nodular keloids and were compared to control fibroblasts from healthy skin. Transcriptional profiling of fibroblasts identified a total of 834 differentially expressed genes between nodular and extensive keloids. Quantification of ECM‐associated gene expression by RT‐qPCR brought evidence that central reticular fibroblasts of nodular keloids are the population which synthesize higher levels of mature collagens, TGFβ, HIF1α and αSMA as compared to control skin, suggesting that this central deep region is the nucleus of ECM production with a centrifuge extension in keloids. Although no significant variations were found for basal proliferation, migration of peripheral fibroblasts from extensive keloids was higher than that of central ones and from nodular cells. Moreover, these peripheral fibroblasts from extensive keloids exhibited higher traction forces than central cells, control fibroblasts and nodular ones. Altogether, studying fibroblast features demonstrate keloid heterogeneity, leading to a better understanding of keloid pathophysiology and treatment adaptation.

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“…Apart from the SP-NK1R pathway, other possible mechanisms of action of BTX-A in inhibiting hypertrophic scars need to be explored. Multiple pathways such as TGFβ/Smad, TGF-β/MMPs and BMP4/Smad were reported to be mediated by BTX-A in the regulation of collagen (41)(42)(43). Furthermore, BTX-A has also been proved to reduce the secretion of pro-inflammatory factors by targeting SNAP23, SNAP25 and TLR2/MyD88 signaling (44,45).…”

Section: Discussionmentioning

confidence: 99%

Dramatic Effect of Botulinum Toxin Type A on Hypertrophic Scar: A Promising Therapeutic Drug and Its Mechanism Through the SP-NK1R Pathway in Cutaneous Neurogenic Inflammation

Zhang

et al. 2022

Front. Med.

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BackgroundHypertrophic scar formation may be related to cutaneous neurogenic inflammation (CNI) through the substance P-neurokinin 1 receptor (SP-NK1R) signaling pathway. As a widely used drug in aesthetic clinical work, botulinum toxin type A (BTX-A) has a therapeutic effect on scars, but the actual mechanism remains unclear. This study aimed to clarify the potential mechanism by which BTX-A inhibits CNI in hypertrophic scars both in vitro and in vivo.MethodsTissue samples were obtained from surgical excisions. Immunohistological analysis was used to locate SP in human hypertrophic scars and normal skin. RT-PCR and western blot analysis were used to evaluate the expression of collagens after SP/BTX-A treatment. A rabbit ear scar model was used to explore the in vivo effect of BTX-A on scar treatment.ResultsSP and NK-1R were overexpressed in hypertrophic scars compared to normal skin tissues. Collagen secretion of hypertrophic scar-derived fibroblasts increased with increasing doses of SP. However, BTX-A may downregulate collagen expression through SP-NK1R pathway with or without the presence of SP inducing agent capsaicin. Meanwhile, SP inhibited the expression of NK-1R, and this inhibition was blocked by pretreatment with BTX-A. In vivo, intralesional BTX-A injection can also reduce the volume of scars and inhibit collagen secretion. Capsaicin may cause more severe scar manifestations, while the therapeutic effect of BTX-A remains.ConclusionOur research confirms that CNI stimulates fibroblasts during scar formation, while BTX-A can reduce collagen secretion by inhibiting the SP-NK1R signaling pathway, thus identifying a novel therapeutic target for this benign solid skin tumor.

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

Cited by 11 publications

References 23 publications

Microneedling combined with botulinum toxin-A versus microneedling combined with platelet-rich plasma in treatment of atrophic acne scars: a comparative split face study

Microneedling combined with botulinum toxin-A versus microneedling combined with platelet-rich plasma in treatment of atrophic acne scars: a comparative split face study

Evidence of inter‐ and intra‐keloid heterogeneity through analysis of dermal fibroblasts: A new insight in deciphering keloid physiopathology

Dramatic Effect of Botulinum Toxin Type A on Hypertrophic Scar: A Promising Therapeutic Drug and Its Mechanism Through the SP-NK1R Pathway in Cutaneous Neurogenic Inflammation

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