Exosomes derived from Mesenchymal Stem cells alleviate the expressions of liver Fibrogenic genes in human hepatic stellate cells

Backgrounds: Hepatic fibrosis is one of the main reasons for mortality in the world, and there isno definite cure for it. The lack of effective treatments for Hepatic fibrosis is a major globalproblem. When hepatic stellate cells (HSCs) activate, the expression of TGF-β and αSMA(Hepatic Fibrogenic genes) will increase, which leads to hepatic fibrosis. At present, there islittle information on the action mechanism of exosomes derived from Whartons’ jellymesenchymal stem cells (WJ-MSCs) in the treatment of liver fibrosis. So we decided to study theeffect of exosomes of WJ-MSCs in the clinic and remedy.In this study, we investigated the effects of exosomes on genes involved in hepatic fibrosisprogression in the cholesterol-activated human HSCs.Materials and Methods: In this experimental study, the HSCs were cultured in a DMEMmedium with ۱۰% Fetal Bovine Serum, and then the cells were treated with ۱۰۰μM Cholesterolto be activated. After that, the cells were treated with the ۲۰μM exosomes. Finally, QuantitativeReal-time PCR and Western blotting techniques were performed.Results: Exosome treatment significantly reduced the expression of TGF-β and αSMA genes inthe cholesterol-activated HSCs (P< ۰.۰۵). Exosomes Treatment decreased the activation of HSCsby inhibiting the level of Smad۳C phosphorylation.Conclusion: In summary, treatment with exosomes of WJ-MSCs reduced HSC activation invitro. The relevant mechanism is through inhibition of the TGF-β / Smad۳C signaling pathway.According to these results, exosomes derived from WJ-MSCs can be introduced as a potentialtherapeutic agent for the treatment of hepatic fibrosis.

کلیدواژه ها:

Hepatic Fibrosis ، Exosomes ، TGFβ ، αSMA ، HSCs