Exosomes of Whartons’ jelly mesenchymal stem cell reduce the NOX genes in TGF-β-induced hepatic fibrosis

Objective(s): Activated cells which are called star-shaped cells, are some of the key factors in the development of liver fibrosis. Activation of NADPH oxidase (NOX) is associated with increased HSCs activity and progression of hepatic fibrosis. In this study, the effects of human exosomes derived from WJ-MSCs on NOX۱, NOX۲, and NOX۴ gene expression in TGF-β-induced hepatic fibrosis were investigated.Materials and Methods: LX۲ cell line was treated with ۲ ng/ml TGF-β for ۲۴ hr, in order to induce liver fibrosis after starvation. In the next step, the cells were treated with several concentrations of the exosomes derived from WJ-MSCs (۱۰, ۲۰, ۳۰, ۴۰, and ۵۰ μg/ml). Finally, Smad۳C phosphorylated protein expression level and NOX۱, NOX۲, and NOX۴ gene expression levels were measured.Results: The results demonstrated that the level of NOX۱, NOX۲, and NOX۴ mRNA expressions decreased significantly during ۲۴ hrs at concentrations of ۴۰ and ۵۰ μg/ml of WJ-MSCs exosomes in TGF-β-induced-HSCs. The p-Smad۳C proteins were significantly decreased (fold change: ۱.۸۳, P-value<۰.۰۵) after exposure to WJ-MSC-derived exosomes. Conclusion: Treatment with exosomes prevents further activation of HSCs by inhibiting the level of Smad۳C phosphorylation. The experimental data of our study suggested that in liver fibrosis, the protection of HSCs activation against TGF-β by inhibiting the NOX pathway via human exosomes of WJ-MSCs is extremely important. It needs further research as a treatment method.

کلیدواژه ها:

Exosome ، HSCs/LX۲ ، Liver fibrosis ، TGF β/Smad۳C and NOXs ، WJ-MSCs