pretreatment of exosomes derived from hucmscs with lps ameliorates liver fibrosis by inhibiting the smad3c through upregulating mir-126 in the hsc-t6 cell line

Background: activated hepatic stellate cells (hsc) through the tgf-β signaling pathway are likely to exacerbate liver fibrosis, which is a later stage of nash, a condition in which, in addition to hsc activation, the overexpression of extracellular matrix (ecm) proteins, specifically collagen-i α and α-sma, is expected. microrna-126a, a modulator of hsc activation, influences the phosphorylation of smad2/3. objectives: this study aimed to investigate the impact of exosomes on mirnas implicated in the progression of liver fibrosis by focusing on the role of mir-126a in the hsc-t6 cell line. methods: in the present study, we investigated the effects of exosomes derived from lps-stimulated mesenchymal stem cells (mscs) on the expression of mir-126a and the phosphorylation of smad3c in the hsc-t6 cell line. first, hsc-t6 cells were cultured in dmem supplemented with 10% fbs. next, we isolated exosomes derived from mscs using the exocib kit. finally, we examined the gene expression levels of collagen-iα, α-sma, and mir-126a using real-time pcr. results: the results showed that treatment with tgfβ1 increased the phosphorylation of p-smad3c (p < 0.0001), as well as the expression of α-sma and collagen-iα. conversely, mir-126a expression was down-regulated after treatment with tgfβ1 (p < 0.01). however, exposure to lps-treated msc-derived exosomes resulted in a significant decrease in the levels of p-smad3c phosphorylation (p < 0.001) and the gene expression of α-sma and collagen-iα, accompanied by the up-regulation of mir-126a (p < 0.05). conclusions: based on our observations, mscs-derived exosomes were able to reduce the expression of the genes associated with hepatic fibrosis, such as collagen-iα and α-sma. furthermore, exosomes inhibited smad3c phosphorylation by increasing mir-126a expression, ultimately hindering the progression of liver fibrosis. therefore, exosomes should be recognized as a valuable and beneficial therapeutic tool for liver fibrosis.