Antifibrotic effects and mechanisms of mesenchymal stem cell-derived exosomes in a systemic sclerosis mouse model: Possible contribution of miR-196b-5p.
Animals
Bleomycin
/ administration & dosage
Cells, Cultured
Collagen Type I
/ metabolism
Disease Models, Animal
Exosomes
/ metabolism
Female
Fibroblasts
/ metabolism
Fibrosis
Humans
Mesenchymal Stem Cells
/ cytology
Mice
MicroRNAs
/ metabolism
Receptor, Transforming Growth Factor-beta Type I
/ metabolism
Scleroderma, Systemic
/ chemically induced
Skin
/ cytology
Transforming Growth Factor beta
/ metabolism
Bleomycin
Fibrosis
Mesenchymal stem cells
Micro RNA
Systemic sclerosis
Journal
Journal of dermatological science
ISSN: 1873-569X
Titre abrégé: J Dermatol Sci
Pays: Netherlands
ID NLM: 9011485
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
received:
02
06
2021
revised:
01
08
2021
accepted:
22
08
2021
pubmed:
5
9
2021
medline:
16
2
2022
entrez:
4
9
2021
Statut:
ppublish
Résumé
Systemic sclerosis (SSc) is a connective tissue disorder characterized by the development of fibrosis in the skin and internal organs. Increasing evidence suggests that mesenchymal stem cells (MSCs) can be used to a treatment for fibrotic diseases. Recent studies have demonstrated that some of the biological effects of MSCs are due to the secretion of exosomes. However, the precise mechanisms underlying MSCs-derived exosomes in skin fibrosis are not well understood. We aimed to elucidate the effect of MSCs-derived exosomes on skin fibrosis in SSc and the mechanism underlying their inhibitory action on fibrosis. Exosome was collected from MSCs by ultracentrifugation method. We examined the suppressive effect of MSCs-derived exosome on skin fibrosis in bleomycin-induced SSc mouse model. Skin samples from the injected site were collected for further examination, and micro-RNA analysis of MSCs-derived exosome was performed. Injection of MSCs-derived exosomes significantly inhibited bleomycin-induced dermal fibrosis in mice. MSCs-derived exosomes significantly reduced the amount of collagen and the number of α-SMA This study demonstrated that inhibition of collagen type I expression by miR-196b-5p in exosomes might be one of the mechanisms by which MSCs suppress skin fibrosis in an SSc mouse model.
Sections du résumé
BACKGROUND
BACKGROUND
Systemic sclerosis (SSc) is a connective tissue disorder characterized by the development of fibrosis in the skin and internal organs. Increasing evidence suggests that mesenchymal stem cells (MSCs) can be used to a treatment for fibrotic diseases. Recent studies have demonstrated that some of the biological effects of MSCs are due to the secretion of exosomes. However, the precise mechanisms underlying MSCs-derived exosomes in skin fibrosis are not well understood.
OBJECTIVE
OBJECTIVE
We aimed to elucidate the effect of MSCs-derived exosomes on skin fibrosis in SSc and the mechanism underlying their inhibitory action on fibrosis.
METHODS
METHODS
Exosome was collected from MSCs by ultracentrifugation method. We examined the suppressive effect of MSCs-derived exosome on skin fibrosis in bleomycin-induced SSc mouse model. Skin samples from the injected site were collected for further examination, and micro-RNA analysis of MSCs-derived exosome was performed.
RESULTS
RESULTS
Injection of MSCs-derived exosomes significantly inhibited bleomycin-induced dermal fibrosis in mice. MSCs-derived exosomes significantly reduced the amount of collagen and the number of α-SMA
CONCLUSION
CONCLUSIONS
This study demonstrated that inhibition of collagen type I expression by miR-196b-5p in exosomes might be one of the mechanisms by which MSCs suppress skin fibrosis in an SSc mouse model.
Identifiants
pubmed: 34479773
pii: S0923-1811(21)00199-7
doi: 10.1016/j.jdermsci.2021.08.006
pii:
doi:
Substances chimiques
Col1a2 protein, mouse
0
Collagen Type I
0
MIRN196 microRNA, mouse
0
MicroRNAs
0
Transforming Growth Factor beta
0
Bleomycin
11056-06-7
Receptor, Transforming Growth Factor-beta Type I
EC 2.7.11.30
Tgfbr1 protein, mouse
EC 2.7.11.30
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
39-47Informations de copyright
Copyright © 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors have no conflict of interest to declare.