MiRNA-29b accelerates the PDGF in exosomes and stimulates hepatic stellate cells to promote liver fibrosis in biliary atresia

Background Biliary atresia (BA) is one of the most common liver diseases in infants and young children. Its etiology and pathogenesis are still unclear. The purpose was to investigate the mechanism by which the highly expressed miRNA-29b in exosomes regulates the high expression of PDGF through methylation, hepatic stellate cell activation, and participation in the hepatic fibrosis of BA. Methods In previous experiments, peripheral blood exosomes of children with biliary atresia and cholangiectasia (CC) were analyzed, and it was found that miRNA-29b was highly expressed in the exosomes of children with BA. Meanwhile, PDGF was highly expressed.Jurkat cells were infected with lentivirus overexpressing miRNA-29b, and the exosomes of Jurkat cells were extracted and cocultured with hepatic stellate cells (LX-2). Results DNMT3a and DNMT3b expression was downregulated and PDGFA expression was upregulated in the miR-29b overexpression group, which activated hepatic stellate cells. DNMT3a/3b was identified as the target gene of miR-29b by luciferase assays. Downregulation of DNMTs resulted in hypomethylation of the PDGF promoter region and high expression of PDGFA. Western blot analysis showed increased expression of COL1A1 and α-SMA, and CCK-8 analysis showed increased proliferation of LX-2 cells. Conclusions Our study showed that miRNA-29b was highly expressed in peripheral blood exosomes and that PDGFA was highly expressed in liver tissues in children with BA. Exosomes overexpressing miRNA-29b caused hypomethylation of the DNA promoter region of PDGFA in hepatic stellate cells, promoted the high expression of PDGFA, activated hepatic stellate cells, and participated in BA-associated liver fibrosis, elucidating the pathogenesis of BA.