Cargando…

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 f...

Descripción completa

Detalles Bibliográficos
Autores principales: Afarin, Reza, Behdarvand, Tahereh, Shakerian, Elham, Salehipour Bavarsad, Samaneh, Rashidi, Mojtaba
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mashhad University of Medical Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9742568/
https://www.ncbi.nlm.nih.gov/pubmed/36544529
http://dx.doi.org/10.22038/IJBMS.2022.66802.14649
_version_ 1784848550312542208
author Afarin, Reza
Behdarvand, Tahereh
Shakerian, Elham
Salehipour Bavarsad, Samaneh
Rashidi, Mojtaba
author_facet Afarin, Reza
Behdarvand, Tahereh
Shakerian, Elham
Salehipour Bavarsad, Samaneh
Rashidi, Mojtaba
author_sort Afarin, Reza
collection PubMed
description 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 NOX1, NOX2, and NOX4 gene expression in TGF-β-induced hepatic fibrosis were investigated. MATERIALS AND METHODS: LX2 cell line was treated with 2 ng/ml TGF-β for 24 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 (10, 20, 30, 40, and 50 μg/ml). Finally, Smad3C phosphorylated protein expression level and NOX1, NOX2, and NOX4 gene expression levels were measured. RESULTS: The results demonstrated that the level of NOX1, NOX2, and NOX4 mRNA expressions decreased significantly during 24 hrs at concentrations of 40 and 50 μg/ml of WJ-MSCs exosomes in TGF-β-induced-HSCs. The p-Smad3C proteins were significantly decreased (fold change: 1.83, P-value<0.05) after exposure to WJ-MSC-derived exosomes. CONCLUSION: Treatment with exosomes prevents further activation of HSCs by inhibiting the level of Smad3C 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.
format Online
Article
Text
id pubmed-9742568
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Mashhad University of Medical Sciences
record_format MEDLINE/PubMed
spelling pubmed-97425682022-12-20 Exosomes of Whartons’ jelly mesenchymal stem cell reduce the NOX genes in TGF-β-induced hepatic fibrosis Afarin, Reza Behdarvand, Tahereh Shakerian, Elham Salehipour Bavarsad, Samaneh Rashidi, Mojtaba Iran J Basic Med Sci Original Article 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 NOX1, NOX2, and NOX4 gene expression in TGF-β-induced hepatic fibrosis were investigated. MATERIALS AND METHODS: LX2 cell line was treated with 2 ng/ml TGF-β for 24 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 (10, 20, 30, 40, and 50 μg/ml). Finally, Smad3C phosphorylated protein expression level and NOX1, NOX2, and NOX4 gene expression levels were measured. RESULTS: The results demonstrated that the level of NOX1, NOX2, and NOX4 mRNA expressions decreased significantly during 24 hrs at concentrations of 40 and 50 μg/ml of WJ-MSCs exosomes in TGF-β-induced-HSCs. The p-Smad3C proteins were significantly decreased (fold change: 1.83, P-value<0.05) after exposure to WJ-MSC-derived exosomes. CONCLUSION: Treatment with exosomes prevents further activation of HSCs by inhibiting the level of Smad3C 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. Mashhad University of Medical Sciences 2022-12 /pmc/articles/PMC9742568/ /pubmed/36544529 http://dx.doi.org/10.22038/IJBMS.2022.66802.14649 Text en https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Afarin, Reza
Behdarvand, Tahereh
Shakerian, Elham
Salehipour Bavarsad, Samaneh
Rashidi, Mojtaba
Exosomes of Whartons’ jelly mesenchymal stem cell reduce the NOX genes in TGF-β-induced hepatic fibrosis
title Exosomes of Whartons’ jelly mesenchymal stem cell reduce the NOX genes in TGF-β-induced hepatic fibrosis
title_full Exosomes of Whartons’ jelly mesenchymal stem cell reduce the NOX genes in TGF-β-induced hepatic fibrosis
title_fullStr Exosomes of Whartons’ jelly mesenchymal stem cell reduce the NOX genes in TGF-β-induced hepatic fibrosis
title_full_unstemmed Exosomes of Whartons’ jelly mesenchymal stem cell reduce the NOX genes in TGF-β-induced hepatic fibrosis
title_short Exosomes of Whartons’ jelly mesenchymal stem cell reduce the NOX genes in TGF-β-induced hepatic fibrosis
title_sort exosomes of whartons’ jelly mesenchymal stem cell reduce the nox genes in tgf-β-induced hepatic fibrosis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9742568/
https://www.ncbi.nlm.nih.gov/pubmed/36544529
http://dx.doi.org/10.22038/IJBMS.2022.66802.14649
work_keys_str_mv AT afarinreza exosomesofwhartonsjellymesenchymalstemcellreducethenoxgenesintgfbinducedhepaticfibrosis
AT behdarvandtahereh exosomesofwhartonsjellymesenchymalstemcellreducethenoxgenesintgfbinducedhepaticfibrosis
AT shakerianelham exosomesofwhartonsjellymesenchymalstemcellreducethenoxgenesintgfbinducedhepaticfibrosis
AT salehipourbavarsadsamaneh exosomesofwhartonsjellymesenchymalstemcellreducethenoxgenesintgfbinducedhepaticfibrosis
AT rashidimojtaba exosomesofwhartonsjellymesenchymalstemcellreducethenoxgenesintgfbinducedhepaticfibrosis