Lab Anim Res.  2011 Jun;27(2):161-169. 10.5625/lar.2011.27.2.161.

Transcriptome Analysis of the Effects of Gomisin A on the Recovery of Carbon Tetrachloride-Induced Damage in Rat Liver

Affiliations
  • 1Department of Horticultural Bioscience, College of Natural Resource & Life Science, Pusan National University, Miryang, Republic of Korea. ypark@pusan.ac.kr
  • 2Department of Plant Bioscience, College of Natural Resource & Life Science, Pusan National University, Miryang, Republic of Korea.
  • 3Department of Life Science & Environmental Biochemistry, College of Natural Resource & Life Science, Pusan National University, Miryang, Republic of Korea.
  • 4Department of Biomaterials Science, College of Natural Resource & Life Science, Pusan National University, Miryang, Republic of Korea.

Abstract

Gomisin A possesses a hepatic function-facilitating property in liver-injured rats. Its preventive action on carbon tetrachloride-induced cholestasis is due to maintenance of the function of the bile acids-independent fraction. To investigate alterations in gene expression after gomisin A treatment on injured rat liver, DNA microarray analyses were performed on a Rat 44K 4-Plex Gene Expression platform with duplicated reactions after gomisin A treatment. We identified 255 up-regulated and 230 down-regulated genes due to the effects of gomisin A on recovery of carbon tetrachloride-induced rat liver damage. For functional characterization of these genes, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes biochemical pathways analyses were performed. Many up-regulated or down-regulated genes were related to cell cycle or focal adhesion and cell death genes, respectively. Our microarray experiment indicated that the liver repair mechanism induced by gomisin A was strongly associated with increased gene expressions related to cell cycle and suppression of the gene expression related in cell death.

Keyword

Gomisin A; carbon tetrachloride; hepatic necrosis; microarray; transcriptome

MeSH Terms

Animals
Bile
Carbon
Carbon Tetrachloride
Cell Cycle
Cell Death
Cholestasis
Cyclooctanes
Dioxoles
Focal Adhesions
Gene Expression
Gene Expression Profiling
Genome
Lignans
Liver
Oligonucleotide Array Sequence Analysis
Rats
Transcriptome
Carbon
Carbon Tetrachloride
Cyclooctanes
Dioxoles
Lignans

Figure

  • Figure 1 Histology of liver tissue. A, vehicle; B, gomisin A alone; C, carbon tetrachloride (CCl4) alone; D, CCl4+gomisin A. The hepatocytic morphology on the liver section stained with hematoxylin and eosin was observed with light microscope at ×400. Arrows indicate the necrotic hepatocytes.

  • Figure 2 Dendrograms showing strategies for identifying specifically regulated genes in the process of gomisin A-induced recovery of rat liver tissues; 255 up-regulated (A) and 230 down-regulated (B) genes were identified. In A, <1 (in CT) and <2 (in GT) indicate the number of genes that did not showed significant up-regulation in CT and GT groups, respectively, and >2 (in GCT) indicates the number of genes that showed significant up-regulation in GCT group. In B, >1 (in CT) and >0.5 (in GT) indicate the number of genes that did not showed significant down-regulation in CT and GT treated groups, respectively, and >0.5 (in GCT) indicates the number of genes that showed significant down-regulation in GCT group.

  • Figure 3 Hierarchical clustering of 488 genes selected as shown in Figure 1. Y-axis shows the list of genes and X-axis shows control and samples. Red fields show un-regulation of genes (absolute difference) and green fields show down-regulation of genes. U, UT group; C, CT group; G, GT group; GC, GCT group.

  • Figure 4 Pathway assignment of the important genes based on KEGG. The genes of up-regulation in cell cycle pathway (A) and the genes of down-regulation in TGF-β signaling pathway (B) were determined by KEGG pathway. The genes found in our microarray analysis were labeled by star symbols.


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