the up-regulation of mir-146a and mir-29b via exosomes protects against liver fibrosis by inhibiting the tgf-β/smad3c signaling pathway

Background: hepatic fibrosis is characterized by the increased proliferation and activation of hepatic stellate cells. transforming growth factor-beta (tgf-β) stimulates these stellate cells, leading to the development of liver fibrosis. microrna-146a and microrna-29b have been identified as significant regulatory factors in fibrogenesis. objectives: in this study, we investigated the ability of exosomes to alleviate liver fibrosis by enhancing the antifibrotic effects of mir-146a and mir-29b. methods: the lx-2 cells were exposed to tgf-β for 24 hours. subsequently, the cells were treated with exosomes for an additional 24 hours. following this treatment, the mrna expression levels of alpha-smooth muscle actin (α-sma), collagen1α, mir-146a, and mir-29b, as well as the protein levels of phosphorylated smad3 (p-smad3), were evaluated. results: the findings revealed a significant elevation in the expression of α-sma (5.37-fold, p < 0.0001) and collagen1α (3.87-fold, p < 0.001) genes, as well as an increase in the levels of p-smad3 protein (5.87-fold, p < 0.0001) in the presence of tgf-β. moreover, the expression of mir-146a (0.54-fold, p < 0.05) and mir-29b (0.46-fold, p < 0.01) genes exhibited a notable decrease compared to the control group under the influence of tgf-β. in our investigation, the administration of exosomes effectively mitigated the tgf-β-induced up-regulation of α-sma (3.26-fold, p < 0.01) and collagen1α (1.76-fold, p < 0.01) genes, as well as the p-smad3 protein (2.86-fold, p < 0.01), in lx-2 cells. conclusions: our results suggest that exosomes effectively impede the continuous activation of hepatic stellate cells (hscs) by enhancing the antifibrotic effects mediated by mir-146a and mir-29b. moreover, exosomes demonstrate inhibitory effects on the tgf-β/smad3 signaling pathway, resulting in decreased extracellular matrix (ecm) accumulation in the context of in vitro liver fibrosis.