Exosomes of mesenchymal stem cells reduce cholesterol-induced hepatic fibrogenesis by inhibiting TGF-β/Smad3 signaling pathway in LX2 cells

Abstract

Abstract Dietary cholesterol is involved in the development of liver fibrosis, because free cholesterol accumulates in HSCs, can lead to Hepatic stellate cells (HSCs) sensitization to TGFβ. HSCs play a crucial role in the liver fibrosis process. This pathway can be targeted by anti-fibrotic therapies. MSCs-derived exosomes are known as the new mechanism of cell-to-cell communication which shows that exosomes have the potential to be used as a new treatment for diseases. In this study, we investigated the ability of exosomes of Whartons’ jelly of MSCs (WJ-MSCs) to reduce cholesterol-induced liver fibrosis in the LX2 cell line. MSCs were isolated from Wharton's jelly of the umbilical cord and the exosome was extracted from the supernatant of culture. LX2 cell line was cultured in DMEM medium with 10% FBS, then cells were treated with 75 and 100 µM concentrations of cholesterol for 24 h, respectively. The expression mRNA of genes of TGF-β, αSMA, collagen1α, and the level of Smad3 protein were measured to assess liver fibrosis. Exosome treatment significantly reduced the expression of TGF-β, α-SMA, collagen1α genes. Treatment with exosomes prevents the activation of HSCs by inhibiting the phosphorylation of Smad3 protein. Cholesterol increases the expression of TGF-β, α-SMA, collagen1α genes by increasing the phosphorylation of Smad3 protein.We observed that the exosomes of WJ-MSCs can inhibit the TGFβ/Smad3 signaling pathway that can prevent further activation of HSCs and progression of liver fibrosis. So, the exosome of WJ-MSCs s will be improving its therapeutic potential for liver failure.