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Liver expression of Nrf2-related genes in different liver diseases |
Ming-Liang Cheng, Yuan-Fu Lu, Hong Chen, Zhong-Yang Shen and Jie Liu |
Guiyang, China
Author Affiliations: The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China (Cheng ML); Key Lab for Basic Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi 563003, China (Lu YF and Liu J); The Institute of Organ Transplantation, The General Hospital of Chinese People's Armed Police Forces, Beijing 100039, China (Chen H and Shen ZY)
Corresponding Author: Ming-Liang Cheng, MD, the Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China (Tel: +86-851- 86752795; Email: Chengml@21cn.com) |
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Abstract 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.
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