Limits...
Identification of serum insulin-like growth factor binding protein 1 as diagnostic biomarker for early-stage alcohol-induced liver disease.

Li HH, Doiron K, Patterson AD, Gonzalez FJ, Fornace AJ - J Transl Med (2013)

Bottom Line: Most notably, the Igfbp1 (Insulin-Like Growth Factor Binding Protein 1) was selected as the best candidate gene for early detection of liver damage since it showed early and continuously enhanced induction during the treatment course.Consistent with the microarray data, both Igfbp1mRNA expression in the liver tissue and the IGFBP1 serum protein levels showed progressive and significant increases over the course of pre-ALD development.The results suggest that in conjunction with other tests, serum IGFBPI protein could provide an easily measured biomarker for early detection of alcohol-induced liver injury in humans.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, 3970 Reservoir Road, NW, New Research Building, Room E504, Washington, DC 20057, USA. af294@georgetown.edu.

ABSTRACT

Background: Alcohol consumption is a major cause of liver disease in humans. The use and monitoring of biomarkers associated with early, pre-clinical stages of alcohol-induced liver disease (pre-ALD) could facilitate diagnosis and treatment, leading to improved outcomes.

Methods: We investigated the pathological, transcriptomic and protein changes in early stages of pre-ALD in mice fed the Lieber-Decarli liquid diet with or without alcohol for four months to identify biomarkers for the early stage of alcohol induced liver injury. Mice were sampled after 1, 2 and 4 months treatment.

Results: Pathological examination revealed a modest increase in fatty liver changes in alcohol-treated mice. Transcriptomics revealed gene alterations at all time points. Most notably, the Igfbp1 (Insulin-Like Growth Factor Binding Protein 1) was selected as the best candidate gene for early detection of liver damage since it showed early and continuously enhanced induction during the treatment course. Consistent with the microarray data, both Igfbp1mRNA expression in the liver tissue and the IGFBP1 serum protein levels showed progressive and significant increases over the course of pre-ALD development.

Conclusions: The results suggest that in conjunction with other tests, serum IGFBPI protein could provide an easily measured biomarker for early detection of alcohol-induced liver injury in humans.

Show MeSH

Related in: MedlinePlus

Changes in gene expression during the four month treatment period as visualized with GEDI analysis using self-organizing maps (SOMs). SOMs were constructed from data for 609 genes. Genes with the most robust induction were deep red while those most repressed were dark blue. Intermediate levels of change lie between these saturated colors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4016206&req=5

Figure 2: Changes in gene expression during the four month treatment period as visualized with GEDI analysis using self-organizing maps (SOMs). SOMs were constructed from data for 609 genes. Genes with the most robust induction were deep red while those most repressed were dark blue. Intermediate levels of change lie between these saturated colors.

Mentions: The genes with altered expression were involved in several essential pathways including metabolism of fatty acids, linoleic acid and arachidonic acid and metabolism of xenobiotics by cytochromes P450 (Figure 1B). To visualize the changes in both induction and repression of gene expression, the genes that had a change of more than 2 fold at two or more time points were subjected to a GEDI analysis. The SOM matrix (Figure 2) shows the time-dependent effect of chronic alcohol intake on liver gene expression.


Identification of serum insulin-like growth factor binding protein 1 as diagnostic biomarker for early-stage alcohol-induced liver disease.

Li HH, Doiron K, Patterson AD, Gonzalez FJ, Fornace AJ - J Transl Med (2013)

Changes in gene expression during the four month treatment period as visualized with GEDI analysis using self-organizing maps (SOMs). SOMs were constructed from data for 609 genes. Genes with the most robust induction were deep red while those most repressed were dark blue. Intermediate levels of change lie between these saturated colors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016206&req=5

Figure 2: Changes in gene expression during the four month treatment period as visualized with GEDI analysis using self-organizing maps (SOMs). SOMs were constructed from data for 609 genes. Genes with the most robust induction were deep red while those most repressed were dark blue. Intermediate levels of change lie between these saturated colors.
Mentions: The genes with altered expression were involved in several essential pathways including metabolism of fatty acids, linoleic acid and arachidonic acid and metabolism of xenobiotics by cytochromes P450 (Figure 1B). To visualize the changes in both induction and repression of gene expression, the genes that had a change of more than 2 fold at two or more time points were subjected to a GEDI analysis. The SOM matrix (Figure 2) shows the time-dependent effect of chronic alcohol intake on liver gene expression.

Bottom Line: Most notably, the Igfbp1 (Insulin-Like Growth Factor Binding Protein 1) was selected as the best candidate gene for early detection of liver damage since it showed early and continuously enhanced induction during the treatment course.Consistent with the microarray data, both Igfbp1mRNA expression in the liver tissue and the IGFBP1 serum protein levels showed progressive and significant increases over the course of pre-ALD development.The results suggest that in conjunction with other tests, serum IGFBPI protein could provide an easily measured biomarker for early detection of alcohol-induced liver injury in humans.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, 3970 Reservoir Road, NW, New Research Building, Room E504, Washington, DC 20057, USA. af294@georgetown.edu.

ABSTRACT

Background: Alcohol consumption is a major cause of liver disease in humans. The use and monitoring of biomarkers associated with early, pre-clinical stages of alcohol-induced liver disease (pre-ALD) could facilitate diagnosis and treatment, leading to improved outcomes.

Methods: We investigated the pathological, transcriptomic and protein changes in early stages of pre-ALD in mice fed the Lieber-Decarli liquid diet with or without alcohol for four months to identify biomarkers for the early stage of alcohol induced liver injury. Mice were sampled after 1, 2 and 4 months treatment.

Results: Pathological examination revealed a modest increase in fatty liver changes in alcohol-treated mice. Transcriptomics revealed gene alterations at all time points. Most notably, the Igfbp1 (Insulin-Like Growth Factor Binding Protein 1) was selected as the best candidate gene for early detection of liver damage since it showed early and continuously enhanced induction during the treatment course. Consistent with the microarray data, both Igfbp1mRNA expression in the liver tissue and the IGFBP1 serum protein levels showed progressive and significant increases over the course of pre-ALD development.

Conclusions: The results suggest that in conjunction with other tests, serum IGFBPI protein could provide an easily measured biomarker for early detection of alcohol-induced liver injury in humans.

Show MeSH
Related in: MedlinePlus