Modulatory effect of rupatadine on mesenchymal stem cell-derived exosomes in hepatic fibrosis in rats: A potential role for miR-200a.
Life Sci
; 324: 121710, 2023 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-37084952
ABSTRACT
AIMS:
Mesenchymal stem cell-derived exosomes (MSC-EXOs) have emerged as a promising approach in regenerative medicine for management of different diseases. However, the maintenance of their efficacy after in vivo transplantation is still a major concern. The present investigation aimed to assess the modulatory effect of rupatadine (RUP) on MSC-EXOs in diethylnitrosamine (DEN)-induced liver fibrosis (LF), and to explore the possible underlying mechanisms. MAINMETHODS:
LF was induced in rats by i.p. injection of DEN (100 mg/kg) once per week for 6 successive weeks. Rats were then treated with RUP (4 mg/kg/day, p.o.) for 4 weeks with or without a single i.v. administration of MSC-EXOs. At the end of the experiment, animals were euthanized and serum and liver were separated for biochemical, and histological measurements. KEYFINDINGS:
The combined MSC-EXOs/RUP therapy provided an additional improvement towards inhibition of DEN-induced LF compared to MSC-EXOs group alone. These outcomes could be mediated through anti-oxidant, anti-inflammatory, anti-necroptotic, and anti-fibrotic effects of RUP which created a more favorable environment for MSC-EXOs homing, and action. This in turn would enhance more effectively miR-200a expression which reduced oxidative stress, inflammation, necroptosis, and subsequently fibrosis as revealed by turning off TGF-ß1/α-SMA expression, and hedgehog axis.SIGNIFICANCE:
The present findings reveal that RUP enhanced the anti-fibrotic efficacy of MSC-EXOs when used as a combined therapy. This was revealed through attenuation of PAF/RIPK3/MLKL/HMGB1, and TGF-ß1/hedgehog signaling pathways with a significant role for miR-200a.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Exossomos
/
Células-Tronco Mesenquimais
Limite:
Animals
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2023
Tipo de documento:
Article