Effects of exosomes of mesenchymal stem cells on cholesterol-induced hepatic fibrogenesis

Objective(s): Free cholesterol in the diet can cause liver fibrosis by accumulating in Hepatic stellate cells (HSCs). The rate of mortality of this disease is high worldwide and there is no definite remedy for it, but might be treated by anti-fibrotic therapies. MSCs-derived exosomes are known as the new mechanism of cell-to-cell communication, showing that exosomes can be used as a new treatment. In this study, we investigated the ability of exosomes of WJ-MSCs as a new remedy to reduce cholesterol-induced liver fibrosis in the LX۲ cell line.Materials and Methods: MSCs were isolated from Wharton’s jelly of the umbilical cord and the exosomes were extracted. The LX۲ cell line was cultured in DMEM medium with ۱۰% FBS, then cells were treated with ۷۵ and ۱۰۰ μM concentrations of cholesterol for ۲۴ hr. The mRNA expression of TGF-β, αSMA, and collagen۱α genes, and the level of Smad۳ protein were measured to assess liver fibrosis. Results: Cholesterol increased the expression of TGF-β, αand -SMA, and collagen۱α genes by increasing the phosphorylation of the Smad۳ protein. Treatment with Exosomes significantly reduced the expression of TGF-β, α-SMA, and collagen۱α genes (fibrosis genes). Treatment with exosomes prevented the activation of HSCs by inhibiting the phosphorylation of the Smad۳ protein. Conclusion: The exosomes of WJ-MSCs can inhibit the TGFβ/Smad۳ signaling pathway preventing further activation of HSCs and progression of liver fibrosis. So, the exosomes of WJ-MSCs s could be introduced as a treatment for liver failure.

کلیدواژه ها:

Cholesterol ، Exosomes ، Fibrosis genes ، Liver fibrosis ، Smad۳ protein