Limits...
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

The liver fibrosis markers HA, LN and PIIINP(A to C) in rhesus monkeys with normal livers (open bar) and alcohol-fed rhesus monkeys with liver fibrosis (solid bar).*Significantly different between control and alcohol-fed rhesus monkeys with liver fibrosis (P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4595740&req=5

f5: The liver fibrosis markers HA, LN and PIIINP(A to C) in rhesus monkeys with normal livers (open bar) and alcohol-fed rhesus monkeys with liver fibrosis (solid bar).*Significantly different between control and alcohol-fed rhesus monkeys with liver fibrosis (P < 0.05).

Mentions: Based on the assessment of histological features in the liver sections, the alcohol-fed animals were categorized by disease stage according to severity: mild, moderate and severe liver steatosis and liver fibrosis. Liver function and blood serum lipids were also analysed, and the numbers of control monkeys, monkeys with mild, moderate and severe liver steatosis and monkeys with fibrosis were 3, 3, 3, 6 and 3 monkeys, respectively (Fig. 4a–h). Blood serum AST concentrations of animals with liver steatosis and fibrosis were elevated compared to the control group (P < 0.05), and an independent predictor of AST/ALT ratios (>1) for mild, moderate and severe liver steatosis and liver fibrosis groups indicated the presence of ALD in those monkeys (Fig. 4d). Meanwhile, plasma GGT concentrations in monkeys with liver fibrosis were significantly increased (P < 0.05), which was identified as an independent predictor of alcohol liver disease (Fig. 4a). The elevated level of plasma AST and the LDH of severe liver steatosis and liver fibrosis groups indicated liver damage in these animals (P < 0.05) (Fig. 4b,e). In addition, serum TG in alcohol-fed animals with symptoms of severe liver steatosis and liver fibrosis were also elevated compared to the control group (P < 0.05) (Fig. 4g). The serum indicators of liver fibrosis are shown in Fig. 5. The concentrations of serum HA and LN in animals with liver fibrosis that was confirmed by histological assessment were elevated compared to those of animals in the control group (P < 0.05). However, no significant difference in PIIINP was observed between control animals and animals with liver fibrosis.


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)

The liver fibrosis markers HA, LN and PIIINP(A to C) in rhesus monkeys with normal livers (open bar) and alcohol-fed rhesus monkeys with liver fibrosis (solid bar).*Significantly different between control and alcohol-fed rhesus monkeys with liver fibrosis (P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: The liver fibrosis markers HA, LN and PIIINP(A to C) in rhesus monkeys with normal livers (open bar) and alcohol-fed rhesus monkeys with liver fibrosis (solid bar).*Significantly different between control and alcohol-fed rhesus monkeys with liver fibrosis (P < 0.05).
Mentions: Based on the assessment of histological features in the liver sections, the alcohol-fed animals were categorized by disease stage according to severity: mild, moderate and severe liver steatosis and liver fibrosis. Liver function and blood serum lipids were also analysed, and the numbers of control monkeys, monkeys with mild, moderate and severe liver steatosis and monkeys with fibrosis were 3, 3, 3, 6 and 3 monkeys, respectively (Fig. 4a–h). Blood serum AST concentrations of animals with liver steatosis and fibrosis were elevated compared to the control group (P < 0.05), and an independent predictor of AST/ALT ratios (>1) for mild, moderate and severe liver steatosis and liver fibrosis groups indicated the presence of ALD in those monkeys (Fig. 4d). Meanwhile, plasma GGT concentrations in monkeys with liver fibrosis were significantly increased (P < 0.05), which was identified as an independent predictor of alcohol liver disease (Fig. 4a). The elevated level of plasma AST and the LDH of severe liver steatosis and liver fibrosis groups indicated liver damage in these animals (P < 0.05) (Fig. 4b,e). In addition, serum TG in alcohol-fed animals with symptoms of severe liver steatosis and liver fibrosis were also elevated compared to the control group (P < 0.05) (Fig. 4g). The serum indicators of liver fibrosis are shown in Fig. 5. The concentrations of serum HA and LN in animals with liver fibrosis that was confirmed by histological assessment were elevated compared to those of animals in the control group (P < 0.05). However, no significant difference in PIIINP was observed between control animals and animals with liver fibrosis.

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