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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

Development of liver steatosis.Histological features in normal rhesus monkey liver (a,b) and alcohol-fed rhesus monkeys with mild (c,d), moderate (e,f) and severe (g,h) liver steatosis (haematoxylin & eosin stain). Obvious hepatocellular vacuolization and macro- and micro-vesicular lipid accumulation can be observed in the liver hepatocytes. The arrow in Fig. 2h indicates infiltration of inflammatory cells.
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f2: Development of liver steatosis.Histological features in normal rhesus monkey liver (a,b) and alcohol-fed rhesus monkeys with mild (c,d), moderate (e,f) and severe (g,h) liver steatosis (haematoxylin & eosin stain). Obvious hepatocellular vacuolization and macro- and micro-vesicular lipid accumulation can be observed in the liver hepatocytes. The arrow in Fig. 2h indicates infiltration of inflammatory cells.

Mentions: Rhesus monkeys were maintained on an alcohol diet for 3 years. Alcohol-fed animals exhibited all of the stages of ALD, based on ultrasound examination and histological assessments. Liver ultrasound images of alcohol-fed rhesus monkeys presented clear liver steatosis and liver fibrosis, in contrast to non-alcohol-fed controls (Fig. 1). Histological examination of H&E stained liver sections revealed the development of mild, moderate and severe liver steatosis with necroinflammatory changes in alcohol-fed rhesus monkeys (Fig. 2). In contrast to the control animals, liver sections from alcohol-fed rhesus monkeys demonstrated steatosis, including hepatocellular vacuolization and macro- and micro-vesicular lipid accumulation in liver hepatocytes (Fig. 2c–h); inflammation and ballooning degeneration were also observed (Fig. 2h). Furthermore, histological examination of Masson stained liver sections demonstrated liver fibrosis in the alcohol-fed rhesus monkeys (Fig. 3). Individual monkey progressed through the stages of steatosis and steatohepatitis at different rates.


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)

Development of liver steatosis.Histological features in normal rhesus monkey liver (a,b) and alcohol-fed rhesus monkeys with mild (c,d), moderate (e,f) and severe (g,h) liver steatosis (haematoxylin & eosin stain). Obvious hepatocellular vacuolization and macro- and micro-vesicular lipid accumulation can be observed in the liver hepatocytes. The arrow in Fig. 2h indicates infiltration of inflammatory cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Development of liver steatosis.Histological features in normal rhesus monkey liver (a,b) and alcohol-fed rhesus monkeys with mild (c,d), moderate (e,f) and severe (g,h) liver steatosis (haematoxylin & eosin stain). Obvious hepatocellular vacuolization and macro- and micro-vesicular lipid accumulation can be observed in the liver hepatocytes. The arrow in Fig. 2h indicates infiltration of inflammatory cells.
Mentions: Rhesus monkeys were maintained on an alcohol diet for 3 years. Alcohol-fed animals exhibited all of the stages of ALD, based on ultrasound examination and histological assessments. Liver ultrasound images of alcohol-fed rhesus monkeys presented clear liver steatosis and liver fibrosis, in contrast to non-alcohol-fed controls (Fig. 1). Histological examination of H&E stained liver sections revealed the development of mild, moderate and severe liver steatosis with necroinflammatory changes in alcohol-fed rhesus monkeys (Fig. 2). In contrast to the control animals, liver sections from alcohol-fed rhesus monkeys demonstrated steatosis, including hepatocellular vacuolization and macro- and micro-vesicular lipid accumulation in liver hepatocytes (Fig. 2c–h); inflammation and ballooning degeneration were also observed (Fig. 2h). Furthermore, histological examination of Masson stained liver sections demonstrated liver fibrosis in the alcohol-fed rhesus monkeys (Fig. 3). Individual monkey progressed through the stages of steatosis and steatohepatitis at different rates.

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