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标题: AAV血清型8介导的肝脏特异性GNMT表达延缓肝细胞癌的进展并防 [打印本页]

作者: StephenW    时间: 2018-9-18 20:36     标题: AAV血清型8介导的肝脏特异性GNMT表达延缓肝细胞癌的进展并防

AAV serotype 8-mediated liver specific GNMT expression delays progression of hepatocellular carcinoma and prevents carbon tetrachloride-induced liver damage

    Cheng-Chieh Fang, Ching-Fen Wu, Yi-Jen Liao, Shiu-Feng Huang, Marcelo Chen & Yi-Ming Arthur Chen

Scientific Reportsvolume 8, Article number: 13802 (2018) | Download Citation
Abstract

Glycine N-methyltransferase (GNMT) is abundantly expressed in normal livers and plays a protective role against tumor formation. GNMT depletion leads to progression of hepatocellular carcinoma (HCC). In this study, we investigated the activity of ectopic GNMT delivered using recombinant adeno-associated virus (AAV) gene therapy in mouse models of liver cirrhosis and HCC. Injection of AAV serotype 8 (AAV8) vector carrying the GNMT gene (AAV8-GNMT) in Gnmt−/− mice increased GNMT expression and downregulated pro-inflammatory responses, resulting in reduced liver damage and incidence of liver tumors. Moreover, AAV8-GNMT resulted in the amelioration of carbon tetrachloride (CCl4)-induced liver fibrosis in BALB/c mice. We showed that AAV8-GNMT protected hepatocytes from CCl4-induced liver damage.  AAV8-GNMT significantly attenuated the levels of pro-fibrotic markers and increased efficiency of hepatocyte proliferation. These results suggest that correction of hepatic GNMT by gene therapy of AAV8-mediated gene enhancement may provide a potential strategy for preventing and delaying development of liver diseases.
作者: StephenW    时间: 2018-9-18 20:36

AAV血清型8介导的肝脏特异性GNMT表达延缓肝细胞癌的进展并防止四氯化碳诱导的肝损伤

    方成杰,吴清芬,廖一仁,黄秀峰,陈洁莹,陈亚明,陈亚明

Scientific Reportsvolume 8,货号:13802(2018)|下载引文
抽象

甘氨酸N-甲基转移酶(GNMT)在正常肝脏中大量表达并且对肿瘤形成起保护作用。 GNMT耗竭导致肝细胞癌(HCC)的进展。在这项研究中,我们研究了使用重组腺相关病毒(AAV)基因治疗在肝硬化和HCC小鼠模型中递送的异位GNMT的活性。在Gnmt - / - 小鼠中注射携带GNMT基因(AAV8-GNMT)的AAV血清型8(AAV8)载体增加了GNMT表达和下调的促炎反应,导致肝损伤和肝肿瘤的发生率降低。此外,AAV8-GNMT导致BALB / c小鼠中四氯化碳(CCl4)诱导的肝纤维化的改善。我们发现AAV8-GNMT保护肝细胞免受CCl4诱导的肝损伤。 AAV8-GNMT显着减弱促纤维化标志物的水平并提高肝细胞增殖的效率。这些结果表明,通过AAV8介导的基因增强的基因疗法校正肝GNMT可以提供预防和延迟肝病发展的潜在策略。




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