Liver expression of Nrf2-related genes in different liver diseases
Liver expression of Nrf2-related genes in different liver diseases
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DOI：
10.1016/s1499-3872(15)60425-8
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发表时间：
2015-10-01
影响因子：
3.3
通讯作者：
Liu, Jie
中科院分区：
文献类型：
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作者：
Cheng, Ming-Liang;Lu, Yuan-Fu;Liu, Jie
背景：KEAP 1-Nrf 2抗氧化信号通路在保护肝脏免受各种损伤中起重要作用。然而，很少有人知道Nrf 2相关基因在人类肝脏中的表达在不同diseases.METHODS：本研究利用正常供体肝组织（n=35），肝细胞癌（HCC，n=24），HBV相关肝硬化（n=27），酒精性肝硬化（n=5）和终末期肝病（n=13）患者的样本。所有肝组织均来自中国北京东方肝移植中心。检测Nrf 2及其相关基因的表达，包括其负调控因子Kelch样ECH相关蛋白1（KEAP 1）、靶基因NAD（P）H-醌氧化还原酶1（NQO 1）、谷氨酸-半胱氨酸连接酶催化亚基（GCLC）和修饰亚基（GCLM）、血红素加氧酶1（HO-1）和过氧化物氧还蛋白1（PRDX-1）。Nrf 2在肝细胞癌中表达降低，在酒精性肝硬化和终末期肝病中表达升高。KEAP 1的表达在所有肝脏样品中均增加。最显著的发现是NQO 1在HCC（18倍）、酒精性肝硬化（6倍）、终末期肝病（5倍）和HBV相关肝硬化（3倍）中的表达增加。与正常肝脏相比，HCC周围的NQO 1 mRNA也高4倍。GCLC mRNA水平仅在HCC中较低，与正常肝脏和HCC周围组织相比。GCLM mRNA水平在HBV相关肝硬化和终末期肝病中较高。HO-1 mRNA水平在除HCC外的所有肝组织中均升高。结论：Nrf 2和Nrf 2相关基因在不同疾病的肝组织中均有异常表达，其中以NQO 1的表达增加最为显著，尤其是在肝癌中。
BACKGROUND: The KEAP1-Nrf2 antioxidant signaling pathway is important in protecting liver from various insults. However, little is known about the expression of Nrf2-related genes in human liver in different diseases.METHODS: This study utilized normal donor liver tissues (n=35), samples from patients with hepatocellular carcinoma (HCC, n=24), HBV-related cirrhosis (n=27), alcoholic cirrhosis (n=5) and end-stage liver disease (n=13). All of the liver tissues were from the Oriental Liver Transplant Center, Beijing, China. The expressions of Nrf2 and Nrf2-related genes, including its negative regulator Kelch-like ECH-associated protein 1 (KEAP1), its targeted gene NAD(P)H-quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC) and modified subunit (GCLM), heme oxygenase 1 (HO-1) and peroxiredoxin-1 (PRDX1) were evaluated.RESULTS: The expression of Nrf2 was decreased in HCC, increased in alcoholic cirrhosis and end-stage liver disease. The expression of KEAP1 was increased in all of the liver samples. The most notable finding was the increased expression of NQO1 in HCC (18-fold), alcoholic cirrhosis (6-fold), end-stage liver disease (5-fold) and HBV-related cirrhosis (3-fold). Peri-HCC also had 4-fold higher NQO1 mRNA as compared to the normal livers. GCLC mRNA levels were lower only in HCC, as compared to the normal livers and peri-HCC tissues. GCLM mRNA levels were higher in HBV-related cirrhosis and end-stage liver disease. HO-1 mRNA levels were increased in all liver tissues except for HCC. Peri-HCC had higher PRDX1 mRNA levels compared with HCC and normal livers.CONCLUSION: Nrf2 and Nrf2-related genes are aberrantly expressed in the liver in different diseases and the increase of NQO1 was the most notable finding, especially in HCC.