Inhibition of the Notch Signaling Pathway Reduces the Differentiation of Hepatic Progenitor Cells into Cholangiocytes in Biliary Atresia
| Title: | Inhibition of the Notch Signaling Pathway Reduces the Differentiation of Hepatic Progenitor Cells into Cholangiocytes in Biliary Atresia |
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| Authors: | Yongzhong Mao, Shaotao Tang, Li Yang, Kang Li |
| Source: | Cellular Physiology and Biochemistry, Vol 49, Iss 3, Pp 1115-1123 (2018) |
| Publisher Information: | Cell Physiol Biochem Press GmbH & Co KG, 2018. |
| Publication Year: | 2018 |
| Collection: | LCC:Physiology LCC:Biochemistry |
| Subject Terms: | Biliary atresia, Notch pathway, Cholangiocyte differentiation, Hepatic progenitor cells, Physiology, QP1-981, Biochemistry, QD415-436 |
| More Details: | Background/Aims: Viral infections, especially with rotavirus, are often considered an initiator of the pathogenesis of biliary atresia (BA). However, the mechanism by which rotavirus induces BA is still unclear. Methods: A BA mouse model was induced in newborn mice by i.p. inoculation with rhesus rotavirus within 6 h of birth. The expression of Notch pathway-associated molecules (JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, DII1, DII3, and DII4) was measured by quantitative PCR and western blot analysis. Bile duct obstruction was detected by hematoxylin and eosin staining and CK-19 immunohistochemical staining. DAPT was used to inhibit the Notch pathway in vivo and in vitro. Results: In the livers of patients with BA and rotavirus-induced BA mice, the expression of JAG1 and Notch2 was significantly increased. Inhibition of the Notch pathway by DAPT in vivo ameliorated bile duct obstruction and delayed BA-induced mortality. The serum levels of inflammation cytokines (TNF-α, IL-2, IL-8, and IL-18) were reduced by inhibiting the Notch pathway. The expression of CK19, Sox9, and EpCAM was significantly increased in BA liver, while DAPT treatment decreased the expression of CK19, Sox9, and EpCAM. Conclusion: Notch activation is involved in the pathogenesis of BA by promoting the differentiation of hepatic progenitor cells into cholangiocytes. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1015-8987 1421-9778 |
| Relation: | https://www.karger.com/Article/FullText/493290; https://doaj.org/toc/1015-8987; https://doaj.org/toc/1421-9778 |
| DOI: | 10.1159/000493290 |
| Access URL: | https://doaj.org/article/634bbaf4ae33447ba3fe3002353f4cf4 |
| Accession Number: | edsdoj.634bbaf4ae33447ba3fe3002353f4cf4 |
| Database: | Directory of Open Access Journals |
| ISSN: | 10158987 14219778 |
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| DOI: | 10.1159/000493290 |
| Published in: | Cellular Physiology and Biochemistry |
| Language: | English |