IL‐8 induces transdifferentiation of mature hepatocytes toward the cholangiocyte phenotype
The adult mammalian liver exhibits a remarkable regenerative capacity, with different modes of regeneration according to the type and extent of injury. Hepatocyte–cholangiocyte biphenotypic liver progenitor cell populations appear under conditions of excessive injury. It has been reported that matur...
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| Format: | Article |
| Language: | English |
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Wiley
2019-12-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.12750 |
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| author | Tokio Sasaki Yuji Suzuki Keisuke Kakisaka Ting Wang Kazuyuki Ishida Akiko Suzuki Hiroaki Abe Tamotsu Sugai Yasuhiro Takikawa |
| author_facet | Tokio Sasaki Yuji Suzuki Keisuke Kakisaka Ting Wang Kazuyuki Ishida Akiko Suzuki Hiroaki Abe Tamotsu Sugai Yasuhiro Takikawa |
| author_sort | Tokio Sasaki |
| collection | DOAJ |
| description | The adult mammalian liver exhibits a remarkable regenerative capacity, with different modes of regeneration according to the type and extent of injury. Hepatocyte–cholangiocyte biphenotypic liver progenitor cell populations appear under conditions of excessive injury. It has been reported that mature hepatocytes can transdifferentiate toward a cholangiocyte phenotype and be a cellular source of progenitor cell populations. Here, we determined that among various plasma cytokines, interleukin (IL)‐8 levels were significantly elevated in acute liver failure and severe acute liver injury patients. In vitro assays revealed that administration of IL‐8 homologues increases the expression of Sry HMG box protein 9 (SOX9). In liver biopsies of acute liver injury patients, we observed the appearance of SOX9‐positive biphenotypic hepatocytes accompanied by elevation of plasma IL‐8 levels. Our results suggest that IL‐8 regulates the phenotypic conversion of mature hepatocytes toward a cholangiocyte phenotype. |
| format | Article |
| id | doaj-art-8ce8b593544c4eb4a49aa6e8ff90387f |
| institution | OA Journals |
| issn | 2211-5463 |
| language | English |
| publishDate | 2019-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj-art-8ce8b593544c4eb4a49aa6e8ff90387f2025-08-20T02:19:22ZengWileyFEBS Open Bio2211-54632019-12-019122105211610.1002/2211-5463.12750IL‐8 induces transdifferentiation of mature hepatocytes toward the cholangiocyte phenotypeTokio Sasaki0Yuji Suzuki1Keisuke Kakisaka2Ting Wang3Kazuyuki Ishida4Akiko Suzuki5Hiroaki Abe6Tamotsu Sugai7Yasuhiro Takikawa8Division of Hepatology Department of Internal Medicine Iwate Medical University School of Medicine Morioka JapanDivision of Hepatology Department of Internal Medicine Iwate Medical University School of Medicine Morioka JapanDivision of Hepatology Department of Internal Medicine Iwate Medical University School of Medicine Morioka JapanDivision of Hepatology Department of Internal Medicine Iwate Medical University School of Medicine Morioka JapanDepartment of Molecular Diagnostic Pathology Iwate Medical University School of Medicine Morioka JapanDivision of Hepatology Department of Internal Medicine Iwate Medical University School of Medicine Morioka JapanDivision of Hepatology Department of Internal Medicine Iwate Medical University School of Medicine Morioka JapanDepartment of Molecular Diagnostic Pathology Iwate Medical University School of Medicine Morioka JapanDivision of Hepatology Department of Internal Medicine Iwate Medical University School of Medicine Morioka JapanThe adult mammalian liver exhibits a remarkable regenerative capacity, with different modes of regeneration according to the type and extent of injury. Hepatocyte–cholangiocyte biphenotypic liver progenitor cell populations appear under conditions of excessive injury. It has been reported that mature hepatocytes can transdifferentiate toward a cholangiocyte phenotype and be a cellular source of progenitor cell populations. Here, we determined that among various plasma cytokines, interleukin (IL)‐8 levels were significantly elevated in acute liver failure and severe acute liver injury patients. In vitro assays revealed that administration of IL‐8 homologues increases the expression of Sry HMG box protein 9 (SOX9). In liver biopsies of acute liver injury patients, we observed the appearance of SOX9‐positive biphenotypic hepatocytes accompanied by elevation of plasma IL‐8 levels. Our results suggest that IL‐8 regulates the phenotypic conversion of mature hepatocytes toward a cholangiocyte phenotype.https://doi.org/10.1002/2211-5463.12750cholangiocyteinterleukin‐8mature hepatocyteSry HMG box protein 9transdifferentiation |
| spellingShingle | Tokio Sasaki Yuji Suzuki Keisuke Kakisaka Ting Wang Kazuyuki Ishida Akiko Suzuki Hiroaki Abe Tamotsu Sugai Yasuhiro Takikawa IL‐8 induces transdifferentiation of mature hepatocytes toward the cholangiocyte phenotype FEBS Open Bio cholangiocyte interleukin‐8 mature hepatocyte Sry HMG box protein 9 transdifferentiation |
| title | IL‐8 induces transdifferentiation of mature hepatocytes toward the cholangiocyte phenotype |
| title_full | IL‐8 induces transdifferentiation of mature hepatocytes toward the cholangiocyte phenotype |
| title_fullStr | IL‐8 induces transdifferentiation of mature hepatocytes toward the cholangiocyte phenotype |
| title_full_unstemmed | IL‐8 induces transdifferentiation of mature hepatocytes toward the cholangiocyte phenotype |
| title_short | IL‐8 induces transdifferentiation of mature hepatocytes toward the cholangiocyte phenotype |
| title_sort | il 8 induces transdifferentiation of mature hepatocytes toward the cholangiocyte phenotype |
| topic | cholangiocyte interleukin‐8 mature hepatocyte Sry HMG box protein 9 transdifferentiation |
| url | https://doi.org/10.1002/2211-5463.12750 |
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