Abstract
The current study tests a hypothesis that nuclear receptor signaling is altered in chronic hepatitis C patients and that the altered pattern is specific to alcohol drinking history. The expression of a panel of more than 100 genes encoding nuclear receptors, coregulators, and their direct/indirect targets was studied in human livers. Gene expression pattern was compared between 15 normal donor livers and 23 hepatitis C virus (HCV) genotype 1-positive livers from patients without a drinking history (matched for age, sex, and body mass index). HCV infection increased the expression of nuclear receptors small heterodimer partner and constitutive androstane receptor (CAR) as well as genes involved in fatty acid trafficking, bile acid synthesis and uptake, and inflammatory response. However, the expression of retinoid X receptor (RXR) α, peroxisomal proliferator-activated receptor (PPAR) α and β as well as steroid regulatory element-binding protein (SREBP)-1c was decreased in HCV-infected livers. Gene expression pattern was compared in chronic hepatitis C patients with and without a drinking history. Alcohol drinking increased the expression of genes involved in fatty acid uptake, trafficking, and oxidation, but decreased the expression of genes responsible for gluconeogenesis. These changes were consistent with reduced fasting plasma glucose levels and altered expression of upstream regulators that include RXRα, PPARα, and CAR. The messenger RNA levels of fibroblast growth factor 21, interleukin-10, and fatty acid synthase, which are all regulated by nuclear receptors, showed independent correlation with hepatic HCV RNA levels. Conclusion: Our findings suggest that those genes and pathways that showed altered expression could potentially be therapeutic targets for HCV infection and/or alcohol drinking-induced liver injury. (HEPATOLOGY 2011)
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1966-1974 |
| Number of pages | 9 |
| Journal | Hepatology |
| Volume | 54 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 2011 |
| Externally published | Yes |
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- Hepatology
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Alteration of hepatic nuclear receptor-mediated signaling pathways in hepatitis C virus patients with and without a history of alcohol drinking. / Wu, Chuanghong; Gilroy, Richard; Taylor, Ryan; Olyaee, Mojtaba; Abdulkarim, Bashar; Forster, Jameson; O'Neil, Maura; Damjanov, Ivan; Wan, Yu-Jui Yvonne.
In: Hepatology, Vol. 54, No. 6, 12.2011, p. 1966-1974.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Alteration of hepatic nuclear receptor-mediated signaling pathways in hepatitis C virus patients with and without a history of alcohol drinking
AU - Wu, Chuanghong
AU - Gilroy, Richard
AU - Taylor, Ryan
AU - Olyaee, Mojtaba
AU - Abdulkarim, Bashar
AU - Forster, Jameson
AU - O'Neil, Maura
AU - Damjanov, Ivan
AU - Wan, Yu-Jui Yvonne
PY - 2011/12
Y1 - 2011/12
N2 - The current study tests a hypothesis that nuclear receptor signaling is altered in chronic hepatitis C patients and that the altered pattern is specific to alcohol drinking history. The expression of a panel of more than 100 genes encoding nuclear receptors, coregulators, and their direct/indirect targets was studied in human livers. Gene expression pattern was compared between 15 normal donor livers and 23 hepatitis C virus (HCV) genotype 1-positive livers from patients without a drinking history (matched for age, sex, and body mass index). HCV infection increased the expression of nuclear receptors small heterodimer partner and constitutive androstane receptor (CAR) as well as genes involved in fatty acid trafficking, bile acid synthesis and uptake, and inflammatory response. However, the expression of retinoid X receptor (RXR) α, peroxisomal proliferator-activated receptor (PPAR) α and β as well as steroid regulatory element-binding protein (SREBP)-1c was decreased in HCV-infected livers. Gene expression pattern was compared in chronic hepatitis C patients with and without a drinking history. Alcohol drinking increased the expression of genes involved in fatty acid uptake, trafficking, and oxidation, but decreased the expression of genes responsible for gluconeogenesis. These changes were consistent with reduced fasting plasma glucose levels and altered expression of upstream regulators that include RXRα, PPARα, and CAR. The messenger RNA levels of fibroblast growth factor 21, interleukin-10, and fatty acid synthase, which are all regulated by nuclear receptors, showed independent correlation with hepatic HCV RNA levels. Conclusion: Our findings suggest that those genes and pathways that showed altered expression could potentially be therapeutic targets for HCV infection and/or alcohol drinking-induced liver injury. (HEPATOLOGY 2011)
AB - The current study tests a hypothesis that nuclear receptor signaling is altered in chronic hepatitis C patients and that the altered pattern is specific to alcohol drinking history. The expression of a panel of more than 100 genes encoding nuclear receptors, coregulators, and their direct/indirect targets was studied in human livers. Gene expression pattern was compared between 15 normal donor livers and 23 hepatitis C virus (HCV) genotype 1-positive livers from patients without a drinking history (matched for age, sex, and body mass index). HCV infection increased the expression of nuclear receptors small heterodimer partner and constitutive androstane receptor (CAR) as well as genes involved in fatty acid trafficking, bile acid synthesis and uptake, and inflammatory response. However, the expression of retinoid X receptor (RXR) α, peroxisomal proliferator-activated receptor (PPAR) α and β as well as steroid regulatory element-binding protein (SREBP)-1c was decreased in HCV-infected livers. Gene expression pattern was compared in chronic hepatitis C patients with and without a drinking history. Alcohol drinking increased the expression of genes involved in fatty acid uptake, trafficking, and oxidation, but decreased the expression of genes responsible for gluconeogenesis. These changes were consistent with reduced fasting plasma glucose levels and altered expression of upstream regulators that include RXRα, PPARα, and CAR. The messenger RNA levels of fibroblast growth factor 21, interleukin-10, and fatty acid synthase, which are all regulated by nuclear receptors, showed independent correlation with hepatic HCV RNA levels. Conclusion: Our findings suggest that those genes and pathways that showed altered expression could potentially be therapeutic targets for HCV infection and/or alcohol drinking-induced liver injury. (HEPATOLOGY 2011)
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UR - http://www.scopus.com/inward/citedby.url?scp=82455162662&partnerID=8YFLogxK
U2 - 10.1002/hep.24645
DO - 10.1002/hep.24645
M3 - Article
C2 - 21898497
AN - SCOPUS:82455162662
VL - 54
SP - 1966
EP - 1974
JO - Hepatology
JF - Hepatology
SN - 0270-9139
IS - 6
ER -