Ni Qi, Ding Kai, Wang Ke-Qi, He Jin, Yin Chuan, Shi Jian, Zhang Xin, Xie Wei-Fen, Shi Yong-Quan
Department of Endocrinology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
FEBS Lett. 2017 Jul;591(13):1947-1957. doi: 10.1002/1873-3468.12689. Epub 2017 Jun 19.
Hepatocyte nuclear factor 1α (HNF1α) is a liver-enriched transcription factor that is critical for the maintenance of hepatocyte function. Our previous studies have demonstrated the therapeutic effects of HNF1α on hepatic fibrosis and hepatocellular carcinoma (HCC) in animals. In this study, we created hepatocyte-specific Hnf1α knockout mice using the Cre-loxP recombination system. The knockout mice display increased fatty acid synthesis in the liver. Moreover, these mice spontaneously develop HCC through fatty liver without cirrhosis. Inflammatory cytokines, such as tumor necrosis factor α and IL-6, are upregulated and accompanied by increased phosphorylation of Akt, p-65 and STAT3 in the livers of HNF1α knockout mice. Our findings suggest that HNF1α plays a crucial role in hepatocyte lipid metabolism and hepatocarcinogenesis.
肝细胞核因子1α（HNF1α）是一种肝脏富集转录因子，对维持肝细胞功能至关重要。我们之前的研究已证明HNF1α对动物肝纤维化和肝细胞癌（HCC）具有治疗作用。在本研究中，我们使用Cre-loxP重组系统创建了肝细胞特异性Hnf1α基因敲除小鼠。这些敲除小鼠肝脏中的脂肪酸合成增加。此外，这些小鼠通过非肝硬化性脂肪肝自发发展为HCC。在HNF1α基因敲除小鼠的肝脏中，肿瘤坏死因子α和IL-6等炎性细胞因子上调，并伴有Akt、p-65和STAT3磷酸化增加。我们的研究结果表明，HNF1α在肝细胞脂质代谢和肝癌发生中起关键作用。
