title: Liver expression of Nrf2-related genes in different liver diseases.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China. Chengml@21cn.com.
authors.forename: Ming-Liang
authors.initials: ML
authors.lastname: Cheng
authors.forename: Yuan-Fu
authors.initials: YF
authors.lastname: Lu
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Zhong-Yang
authors.initials: ZY
authors.lastname: Shen
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D058625:End Stage Liver Disease / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000072019:Kelch-Like ECH-Associated Protein 1; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000235:genetics* / Q000821:virology; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D054464:Peroxiredoxins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D012333:RNA, Messenger; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C000609392:GCLC protein, human; C546365:GCLM protein, human; D005721:Glutamate-Cysteine Ligase