Reticulon 4B (Nogo-B) facilitates hepatocyte proliferation and liver regeneration in mice
| Autor: | Keitaro Tashiro, Lili Gao, E. Scott Swenson, Teruo Utsumi, Yasuko Iwakiri, Bo Liu, Dahai Zhang |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
STAT3 Transcription Factor medicine.medical_specialty Time Factors Nogo Proteins Biology Article Mice Epidermal growth factor Transforming Growth Factor beta Internal medicine mental disorders medicine Animals Hepatectomy Cell Proliferation Mice Knockout Hepatology Epidermal Growth Factor Hepatocyte Growth Factor Interleukin-6 Transforming growth factor beta Liver regeneration Cell biology Liver Regeneration Mice Inbred C57BL medicine.anatomical_structure Endocrinology Liver Hepatocyte Models Animal STAT protein Hepatic stellate cell biology.protein Hepatocytes Hepatocyte growth factor psychological phenomena and processes Myelin Proteins medicine.drug Transforming growth factor Signal Transduction |
| Zdroj: | Hepatology (Baltimore, Md.). 57(5) |
| ISSN: | 1527-3350 |
| Popis: | Nogo-B, also known as reticulon 4B, promotes liver fibrosis and cirrhosis by facilitating the transforming growth factor β (TGF-β) signaling pathway in activated hepatic stellate cells. The aim of this study was to determine the role of Nogo-B in hepatocyte proliferation and liver regeneration. Partial hepatectomy (PHx, 70% resection) was performed in male wild-type (WT) and Nogo-A/B knockout mice (referred to as Nogo-B KO mice). Remnant livers were isolated 2 hours, 5 hours, and 1, 2, 3, 7, and 14 days after PHx. Hepatocyte proliferation was assessed by Ki67 labeling index. Quantitative real-time polymerase chain reaction was performed for genes known to be involved in liver regeneration. Hepatocytes isolated from WT and Nogo-B KO mice were used to examine the role of Nogo-B in interleukin-6 (IL-6), hepatocyte growth factor (HGF), epidermal growth factor (EGF), and TGF-β signaling. Nogo-B protein levels increased in the regenerating livers in a time-dependent manner after PHx. Specifically, Nogo-B expression in hepatocytes gradually spread from the periportal toward the central areas by 7 days after PHx, but receded notably by 14 days. Nogo-B facilitated IL-6/signal transducer and activator of transcription 3 signaling, increased HGF-induced but not EGF-induced hepatocyte proliferation, and tended to reduce TGF-β1–induced suppression of hepatocyte proliferation in cultured hepatocytes. Lack of Nogo-B significantly induced TGF-β1 and inhibitor of DNA binding expression 1 day after PHx and IL-6 and EGF expression 2 days after PHx. Lack of Nogo-B delayed hepatocyte proliferation but did not affect the liver-to-body ratio in the regenerative process. Conclusion: Nogo-B expression in hepatocytes facilitates hepatocyte proliferation and liver regeneration. (HEPATOLOGY 2013) |
| Databáze: | OpenAIRE |
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