Reptin/RUVBL2 is required for hepatocyte proliferation in vivo, liver regeneration and homeostasis
| Autor: | Joaquim Javary, Sylvaine Di Tommaso, Nathalie Dugot-Senant, Jean‐William Dupuis, Violaine Moreau, Zakaria Ezzoukhry, Pierre Dubus, Frédéric Saltel, Samira Benhamouche-Trouillet, Nathalie Allain, Pierre Costet |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_treatment
mTORC1 Biology Mice 03 medical and health sciences 0302 clinical medicine In vivo medicine Animals Hepatectomy Homeostasis Cell Proliferation Hepatology Regeneration (biology) DNA Helicases medicine.disease Liver regeneration Liver Regeneration Cell biology Mice Inbred C57BL medicine.anatomical_structure Liver 030220 oncology & carcinogenesis Hepatocellular carcinoma Hepatocyte Hepatocytes ATPases Associated with Diverse Cellular Activities 030211 gastroenterology & hepatology |
| Zdroj: | Liver International. 41:1423-1429 |
| ISSN: | 1478-3231 1478-3223 |
| DOI: | 10.1111/liv.14886 |
| Popis: | Previous studies have shown that Reptin is overexpressed in hepatocellular carcinoma and that it is necessary for in vitro proliferation and cell survival. However, its pathophysiological role in vivo remains unknown. We aimed to study the role of Reptin in hepatocyte proliferation after regeneration using a liver Reptin knock-out model (ReptinLKO ). Interestingly, hepatocyte proliferation is strongly impaired in ReptinLKO mice 36 hours after partial hepatectomy, associated with a decrease of cyclin-A expression and mTORC1 and MAPK signalling, leading to an impaired liver regeneration. Moreover, in the ReptinLKO model, we have observed a progressive loss of Reptin invalidation associated with an atypical liver regeneration. Hypertrophic and proliferative hepatocytes gradually replace ReptinKO hypotrophic hepatocytes. To conclude, our results show that Reptin is required for hepatocyte proliferation in vivo and liver regeneration and that it plays a crucial role in hepatocyte survival and liver homeostasis. |
| Databáze: | OpenAIRE |
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