Inhibition of skin fibrosis in systemic sclerosis by botulinum toxin B via the suppression of oxidative stress.


Journal

The Journal of dermatology
ISSN: 1346-8138
Titre abrégé: J Dermatol
Pays: England
ID NLM: 7600545

Informations de publication

Date de publication:
Jul 2021
Historique:
revised: 21 03 2021
received: 02 03 2021
accepted: 23 03 2021
pubmed: 12 4 2021
medline: 6 7 2021
entrez: 11 4 2021
Statut: ppublish

Résumé

Oxidative stress has been reported to play an important role in the pathogenesis of skin fibrosis in systemic sclerosis (SSc). We previously identified that botulinum toxin (BTX) injection suppresses pressure ulcer formation in a cutaneous ischemia-reperfusion injury mouse model by regulation of oxidative stress. However, the therapeutic possibility of BTX administration for preventing skin fibrosis in SSc is unclear. The objective of this study was to investigate the effect of BTX-B on skin fibrosis in a murine model of SSc and determine the underlying mechanism. We found that BTX-B injection significantly reduced dermal thickness and inflammatory cell infiltration in bleomycin-induced skin fibrosis lesion in mice. We also identified that the oxidative stress signal detected through bioluminescence in OKD48 mice after bleomycin injection in the skin was significantly decreased by BTX-B. Additionally, mRNA levels of oxidative stress associated factors (NOX2, HO-1, Trx2) were significantly decreased by BTX-B. Apoptotic cells in the lesional skin of bleomycin-treated mice were significantly reduced by BTX-B. Oxidant-induced intracellular accumulation of reactive oxygen species in SSc fibroblasts was also inhibited by BTX-B. In conclusion, BTX-B might improve bleomycin-induced skin fibrosis via the suppression of oxidative stress and inflammatory cells in the skin. BTX-B injection may have a therapeutic effect on skin fibrosis in SSc.

Identifiants

pubmed: 33840125
doi: 10.1111/1346-8138.15888
doi:

Substances chimiques

Bleomycin 11056-06-7

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1052-1061

Subventions

Organisme : JSPS KAKENHI
ID : 18K16019

Informations de copyright

© 2021 Japanese Dermatological Association.

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Auteurs

Hritu Baral (H)

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Akiko Sekiguchi (A)

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Akihiko Uchiyama (A)

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Syahla Nisaa Amalia (S)

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Sahori Yamazaki (S)

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Yuta Inoue (Y)

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Yoko Yokoyama (Y)

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Sachiko Ogino (S)

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Ryoko Torii (R)

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Mari Hosoi (M)

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Ryoko Akai (R)

Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan.

Takao Iwawaki (T)

Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan.

Osamu Ishikawa (O)

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Sei-Ichiro Motegi (SI)

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

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