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Background <p>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 platelet-derived growth factor (PDGF) through methylation, hepatic stellate cell activation, and participation in the hepatic fibrosis of BA.</p> Methods <p>Children with BA and choledochal cysts (CC) had their peripheral blood exosomes examined in previous studies, and it was discovered that miRNA-29b was substantially expressed in the BA children's exosomes. In contrast, 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).</p> Results <p>DNA methyltransferase (DNMT) 3a 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.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月16日

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  • Xilin Liao,
  • Rui Liu,
  • Teng Zhou,
  • Xiaohuan Zhao,
  • Xiangang Xiong,
  • Kaizhi Zhang,
  • Zebing Zheng,
  • Xingrong Xia,
  • Chengyan Tang,
  • Yuan Gong,
  • Qing Du,
  • Lu Huang,
  • Daiwei Zhu,
  • Wankang Zhou,
  • Yuanmei Liu,
  • Zhu Jin

摘要

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 platelet-derived growth factor (PDGF) through methylation, hepatic stellate cell activation, and participation in the hepatic fibrosis of BA.

Methods

Children with BA and choledochal cysts (CC) had their peripheral blood exosomes examined in previous studies, and it was discovered that miRNA-29b was substantially expressed in the BA children's exosomes. In contrast, 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

DNA methyltransferase (DNMT) 3a 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.