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<p>Cholestasis can occur in various acute and chronic liver diseases, with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) being the most common clinical manifestations. Without appropriate treatment, these conditions may ultimately progress to liver cirrhosis and hepatic failure. Therefore, identifying novel therapeutic targets is of great importance.&#xa0;Our previous research had found a gene target named <i>Numb</i> which is a determinant of stem cell fate can increase the anti-cholestatic liver fibrosis (CLF) effect of bone marrow mesenchymal stem cells (BM-MSCs). However, whether the <i>Numb</i> gene or its exon has direct anti-CLF activity is unclear. In this study, an adeno-associated virus (AAV) was used as a gene delivery vector to overexpress the full-length <i>Numb</i> gene directly in the rat liver. In addition, Exon3 was overexpressed to clarify the effective site of <i>Numb</i> gene for comparison.&#xa0;AAV.<i>Numb</i> can alleviate CLF and suppressed the activation of Notch signaling and the differentiation of hepatic progenitor cells (HPCs) into biliary epithelial cells (BECs), and the anti-CLF effect of <i>Numb</i>-Exon3 was similar to that of full-length <i>Numb</i>. The findings revealed that <i>Numb</i> gene may be a new therapeutic target for PBC and that Exon3 may be an effective site.</p>

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Numb-exon3 and full length Numb equivalently alleviate cholestatic liver fibrosis by inhibiting ductular reaction

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月14日

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  • Yan-nan Xu,
  • Meng-yao Zong,
  • Wen Xu,
  • Shi-hao Zhang,
  • Dan-yang Wang,
  • Xin-rui Zheng,
  • Fei-fei Xing,
  • Jun-yi Zhan,
  • Jia-mei Chen,
  • Gao-feng Chen,
  • Ping Liu,
  • Wei Liu,
  • Yong-ping Mu

摘要

Cholestasis can occur in various acute and chronic liver diseases, with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) being the most common clinical manifestations. Without appropriate treatment, these conditions may ultimately progress to liver cirrhosis and hepatic failure. Therefore, identifying novel therapeutic targets is of great importance. Our previous research had found a gene target named Numb which is a determinant of stem cell fate can increase the anti-cholestatic liver fibrosis (CLF) effect of bone marrow mesenchymal stem cells (BM-MSCs). However, whether the Numb gene or its exon has direct anti-CLF activity is unclear. In this study, an adeno-associated virus (AAV) was used as a gene delivery vector to overexpress the full-length Numb gene directly in the rat liver. In addition, Exon3 was overexpressed to clarify the effective site of Numb gene for comparison. AAV.Numb can alleviate CLF and suppressed the activation of Notch signaling and the differentiation of hepatic progenitor cells (HPCs) into biliary epithelial cells (BECs), and the anti-CLF effect of Numb-Exon3 was similar to that of full-length Numb. The findings revealed that Numb gene may be a new therapeutic target for PBC and that Exon3 may be an effective site.