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Rhesus monkey model of liver disease reflecting clinical disease progression and hepatic gene expression analysis.

Wang H, Tan T, Wang J, Niu Y, Yan Y, Guo X, Kang Y, Duan Y, Chang S, Liao J, Si C, Ji W, Si W - Sci Rep (2015)

Bottom Line: Alcoholic liver disease (ALD) is a significant public health issue with heavy medical and economic burdens.The up-regulation of expression of hepatic genes related to liver steatosis (CPT1A, FASN, LEPR, RXRA, IGFBP1, PPARGC1A and SLC2A4) was detected in our rhesus model, as was the down-regulation of such genes (CYP7A1, HMGCR, GCK and PNPLA3) and the up-regulation of expression of hepatic genes related to liver cancer (E2F1, OPCML, FZD7, IGFBP1 and LEF1).These findings will be useful for increasing the understanding of ALD pathogenesis and will benefit the development of new therapeutic procedures and pharmacological reagents for treating ALD.

View Article: PubMed Central - PubMed

Affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, Chin.

ABSTRACT
Alcoholic liver disease (ALD) is a significant public health issue with heavy medical and economic burdens. The aetiology of ALD is not yet completely understood. The development of drugs and therapies for ALD is hampered by a lack of suitable animal models that replicate both the histological and metabolic features of human ALD. Here, we characterize a rhesus monkey model of alcohol-induced liver steatosis and hepatic fibrosis that is compatible with the clinical progression of the biochemistry and pathology in humans with ALD. Microarray analysis of hepatic gene expression was conducted to identify potential molecular signatures of ALD progression. The up-regulation of expression of hepatic genes related to liver steatosis (CPT1A, FASN, LEPR, RXRA, IGFBP1, PPARGC1A and SLC2A4) was detected in our rhesus model, as was the down-regulation of such genes (CYP7A1, HMGCR, GCK and PNPLA3) and the up-regulation of expression of hepatic genes related to liver cancer (E2F1, OPCML, FZD7, IGFBP1 and LEF1). Our results demonstrate that this ALD model reflects the clinical disease progression and hepatic gene expression observed in humans. These findings will be useful for increasing the understanding of ALD pathogenesis and will benefit the development of new therapeutic procedures and pharmacological reagents for treating ALD.

No MeSH data available.


Related in: MedlinePlus

Microarray analyses of the change in hepatic gene expression between control rhesus monkeys and rhesus monkeys with liver steatosis (a) and liver fibrosis (b).
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f6: Microarray analyses of the change in hepatic gene expression between control rhesus monkeys and rhesus monkeys with liver steatosis (a) and liver fibrosis (b).

Mentions: Liver tissues from 3 control monkeys and 6 monkeys showing severe liver steatosis were used for the analysis of hepatic gene expression using the Human Fatty Liver PCR Array; experiments were conducted in triplicate. Genes encoding proteins known to be related to beta-oxidation (CPT1A), lipid metabolism and transport (FASN) in metabolic pathways, adipokine signalling pathway (LEPR, RXRA), insulin signalling pathway metabolic pathways (IGFBP1, PPARGC1A) and a gene involved in non-insulin dependent diabetes mellitus (SLC2A4) were all elevated 3- to 6-fold. Several genes encoding proteins known to be related to cholesterol metabolism and transport (CYP7A1, HMGCR) and genes involved in non-insulin dependent diabetes mellitus (GCK, PNPLA3) were down-regulated 3- to 23-fold (Fig. 6a). Next, liver tissues from 3 control monkeys and 3 alcohol-fed monkeys showing liver fibrosis were used for the analysis of hepatic gene expression using the Human Liver Cancer PCR Array, and the experiments were conducted in triplicate. The expression of genes encoding proteins known to be associated with the cell cycle (E2F1), adhesion and proteolysis (OPCML) and hepatocellular carcinoma (FZD7, IGFBP1 and LEF1) was elevated 3- to 9-fold (Fig. 6b).


Rhesus monkey model of liver disease reflecting clinical disease progression and hepatic gene expression analysis.

Wang H, Tan T, Wang J, Niu Y, Yan Y, Guo X, Kang Y, Duan Y, Chang S, Liao J, Si C, Ji W, Si W - Sci Rep (2015)

Microarray analyses of the change in hepatic gene expression between control rhesus monkeys and rhesus monkeys with liver steatosis (a) and liver fibrosis (b).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4595740&req=5

f6: Microarray analyses of the change in hepatic gene expression between control rhesus monkeys and rhesus monkeys with liver steatosis (a) and liver fibrosis (b).
Mentions: Liver tissues from 3 control monkeys and 6 monkeys showing severe liver steatosis were used for the analysis of hepatic gene expression using the Human Fatty Liver PCR Array; experiments were conducted in triplicate. Genes encoding proteins known to be related to beta-oxidation (CPT1A), lipid metabolism and transport (FASN) in metabolic pathways, adipokine signalling pathway (LEPR, RXRA), insulin signalling pathway metabolic pathways (IGFBP1, PPARGC1A) and a gene involved in non-insulin dependent diabetes mellitus (SLC2A4) were all elevated 3- to 6-fold. Several genes encoding proteins known to be related to cholesterol metabolism and transport (CYP7A1, HMGCR) and genes involved in non-insulin dependent diabetes mellitus (GCK, PNPLA3) were down-regulated 3- to 23-fold (Fig. 6a). Next, liver tissues from 3 control monkeys and 3 alcohol-fed monkeys showing liver fibrosis were used for the analysis of hepatic gene expression using the Human Liver Cancer PCR Array, and the experiments were conducted in triplicate. The expression of genes encoding proteins known to be associated with the cell cycle (E2F1), adhesion and proteolysis (OPCML) and hepatocellular carcinoma (FZD7, IGFBP1 and LEF1) was elevated 3- to 9-fold (Fig. 6b).

Bottom Line: Alcoholic liver disease (ALD) is a significant public health issue with heavy medical and economic burdens.The up-regulation of expression of hepatic genes related to liver steatosis (CPT1A, FASN, LEPR, RXRA, IGFBP1, PPARGC1A and SLC2A4) was detected in our rhesus model, as was the down-regulation of such genes (CYP7A1, HMGCR, GCK and PNPLA3) and the up-regulation of expression of hepatic genes related to liver cancer (E2F1, OPCML, FZD7, IGFBP1 and LEF1).These findings will be useful for increasing the understanding of ALD pathogenesis and will benefit the development of new therapeutic procedures and pharmacological reagents for treating ALD.

View Article: PubMed Central - PubMed

Affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, Chin.

ABSTRACT
Alcoholic liver disease (ALD) is a significant public health issue with heavy medical and economic burdens. The aetiology of ALD is not yet completely understood. The development of drugs and therapies for ALD is hampered by a lack of suitable animal models that replicate both the histological and metabolic features of human ALD. Here, we characterize a rhesus monkey model of alcohol-induced liver steatosis and hepatic fibrosis that is compatible with the clinical progression of the biochemistry and pathology in humans with ALD. Microarray analysis of hepatic gene expression was conducted to identify potential molecular signatures of ALD progression. The up-regulation of expression of hepatic genes related to liver steatosis (CPT1A, FASN, LEPR, RXRA, IGFBP1, PPARGC1A and SLC2A4) was detected in our rhesus model, as was the down-regulation of such genes (CYP7A1, HMGCR, GCK and PNPLA3) and the up-regulation of expression of hepatic genes related to liver cancer (E2F1, OPCML, FZD7, IGFBP1 and LEF1). Our results demonstrate that this ALD model reflects the clinical disease progression and hepatic gene expression observed in humans. These findings will be useful for increasing the understanding of ALD pathogenesis and will benefit the development of new therapeutic procedures and pharmacological reagents for treating ALD.

No MeSH data available.


Related in: MedlinePlus