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Without appropriate treatment, these conditions may ultimately progress to liver cirrhosis and hepatic failure. Therefore, identifying novel therapeutic targets is of great importance.\u00a0Our previous research had found a gene target named\n                    <jats:italic>Numb<\/jats:italic>\n                    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\n                    <jats:italic>Numb<\/jats:italic>\n                    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\n                    <jats:italic>Numb<\/jats:italic>\n                    gene directly in the rat liver. In addition, Exon3 was overexpressed to clarify the effective site of\n                    <jats:italic>Numb<\/jats:italic>\n                    gene for comparison.\u00a0AAV.\n                    <jats:italic>Numb<\/jats:italic>\n                    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\n                    <jats:italic>Numb<\/jats:italic>\n                    -Exon3 was similar to that of full-length\n                    <jats:italic>Numb<\/jats:italic>\n                    . The findings revealed that\n                    <jats:italic>Numb<\/jats:italic>\n                    gene may be a new therapeutic target for PBC and that Exon3 may be an effective site.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-23696-3","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T15:31:27Z","timestamp":1763134287000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Numb-exon3 and full length Numb equivalently alleviate cholestatic liver fibrosis by inhibiting ductular reaction"],"prefix":"10.1038","volume":"15","author":[{"given":"Yan-nan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-yao","family":"Zong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-hao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan-yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-rui","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei-fei","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-yi","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-mei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao-feng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-ping","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"23696_CR1","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1053\/j.gastro.2010.09.004","volume":"139","author":"GM Hirschfield","year":"2010","unstructured":"Hirschfield, G. 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