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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Gene Regulations in HBV-Related Liver Cirrhosis Closely Correlate with Disease Severity

  • Lee, Se-Ram (Department of Chemistry, Dongguk University) ;
  • Kim, So-Youn (Department of Chemistry, Dongguk University)
  • Published : 2007.09.30
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Abstract

Liver cirrhosis (LC) is defined as comprising diffuse fibrosis and regenerating nodules of the liver. The biochemical and anatomical dysfunction in LC results from both reduced liver cell number and portal vascular derangement. Although several studies have investigated dysregulated genes in cirrhotic nodules, little is known about the genes implicated in the pathophysiologic change of LC or about their relationship with the degree of decompensation. Here, we applied cDNA microarray analysis using 38 HBsAg-positive LC specimens to identify the genes dysregulated in HBV-associated LC and to evaluate their relation to disease severity. Among 1063 known cancer- and apoptosis-related genes, we identified 104 genes that were significantly up- (44) or down- (60) regulated in LC. Interestingly, this subset of 104 genes was characteristically correlated with the degree of decompensation, called the Pugh-Child classification (20 Pugh-Child A, 10 Pugh-Child B, and 8 Pugh-Child C). Patient samples from Pugh-Child C exhibited a distinct pattern of gene expression relative to those of Pugh-Child A and B. Especially in Pugh-Child C, genes encoding hepatic proteins and metabolizing enzymes were significantly down-regulated, while genes encoding various molecules related to cell replication were up-regulated. Our results suggest that subsets of genes in liver cells correspond to the pathophysiologic change of LC according to disease severity and possibly to hepatocarcinogenesis.

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References

  1. Anders, R. A., Yerian, L. M., Tretiakova, M., Davison, J. M., Quigg, R. J., Domer, P. H., Hoberg, J. and Hart, J. (2003) cDNA microarray analysis of macroregenerative and dysplastic nodules in end-stage hepatitis C virus-induced cirrhosis. Am. J. Pathol. 162, 991-1000. https://doi.org/10.1016/S0002-9440(10)63893-X
  2. Colonna, M., Samaridis, J. and Angman, L. (2000) Molecular characterization of two novel C-type lectin-like receptors, one of which is selectively expressed in human dendritic cells. Eur. J. Immunol. 30, 697-704. https://doi.org/10.1002/1521-4141(200002)30:2<697::AID-IMMU697>3.0.CO;2-M
  3. Friedman, S. L. (2003) Liver fibrosis - from bench to bedside. J. Hepatol. 38 Suppl 1, 38-53.
  4. Fukuhara, Y., Hirasawa, A., Li, X. K., Kawasaki, M., Fujino, M., Funeshima, N., Katsuma, S., Shiojima, S., Yamada, M., Okuyama, T., Suzuki, S. and Tsujimoto, G. (2003) Gene expression profile in the regenerating rat liver after partial hepatectomy. J. Hepatol. 38, 784-792. https://doi.org/10.1016/S0168-8278(03)00077-1
  5. Honda, M., Kaneko, S., Kawai, H., Shirota, Y. and Kobayashi, K. (2001) Differential gene expression between chronic hepatitis B and C hepatic lesion. Gastroenterology 120, 955-966. https://doi.org/10.1053/gast.2001.22468
  6. Kim, S. and Kim, T. (2003) Selection of optimal internal controls for gene expression profiling of liver disease. Biotechniques 35, 456-458.
  7. Kim, S., Kim, Y., Kim, P., Ha, J., Kim, K., Sohn, M., Yoo, J. S., Lee, J., Kwon, J. A. and Lee, K. N. (2006) Improved sensitivity and physical properties of Sol-gel protein chips using large-scale material screening and selection. Anal. Chem. 78, 7392-7396. https://doi.org/10.1021/ac0520487
  8. Kim, S. and Park, Y. M. (2005) Specific gene expression patterns in liver cirrhosis. Biochem. Biophys. Res. Commun. 334, 681-688. https://doi.org/10.1016/j.bbrc.2005.06.143
  9. Kim, S., Shi, H., Lee, D. K. and Lis, J. T. (2003) Specific SR protein-dependent splicing substrates identified through genomic SELEX. Nucleic Acids Res. 31, 1955-1. https://doi.org/10.1093/nar/gkg286
  10. Lee, S., Jo, M., Lee, J., Koh, S. S. and Kim, S. (2007) Identification of novel universal housekeeping genes by statistical analysis of microarray data. J. Biochem. Mol. Biol. 40, 226-231. https://doi.org/10.5483/BMBRep.2007.40.2.226
  11. Liaw, Y. F., Lin, D. Y., Chen, T. J. and Chu, C. M. (1989) Natural course after the development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Liver 9, 235-241. https://doi.org/10.1055/s-2008-1040516
  12. Montalto, G., Cervello, M., Giannitrapani, L., Dantona, F., Terranova, A. and Castagnetta, L. A. (2002) Epidemiology, risk factors, and natural history of hepatocellular carcinoma. Ann. N. Y. Acad. Sci. 963, 13-20 https://doi.org/10.1111/j.1749-6632.2002.tb04090.x
  13. Nagai, H., Terada, Y., Tajiri, T., Yabe, A., Onda, M., Nagahata, T., Ezura, Y., Minegishi, M., Horiguchi, M., Baba, M., Konishi, N. and Emi, M. (2004) Characterization of liver-cirrhosis nodules by analysis of gene-expression profiles and patterns of allelic loss. J. Hum. Genet. 49, 246-255. https://doi.org/10.1007/s10038-004-0141-8
  14. Okabe, H., Satoh, S., Kato, T., Kitahara, O., Yanagawa, R., Yamaoka, Y., Tsunoda, T., Furukawa, Y. and Nakamura, Y. (2001) Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. Cancer Res. 61, 2129-2137.
  15. Olaso, E. and Friedman, S. L. (1998) Molecular regulation of hepatic fibrogenesis. J. Hepatol. 29, 836-847. https://doi.org/10.1016/S0168-8278(98)80269-9
  16. Otsuka, M., Aizaki, H., Kato, N., Suzuki, T., Miyamura, T., Omata, M. and Seki, N. (2003) Differential cellular gene expression induced by hepatitis B and C viruses. Biochem. Biophys. Res. Commun. 300, 443-447. https://doi.org/10.1016/S0006-291X(02)02861-9
  17. Perera, L. P. (2000) Interleukin 15: its role in inflammation and immunity. Arch. Immunol. Ther. Exp. (Warsz) 48, 457-464.
  18. Pugh, R. N., Murray-Lyon, I. M., Dawson, J. L., Pietroni, M. C. and Williams, R. (1973) Transection of the oesophagus for bleeding oesophageal varices. Br. J. Surg. 60, 646-649. https://doi.org/10.1002/bjs.1800600817
  19. Roncalli, M., Bianchi, P., Grimaldi, G. C., Ricci, D., Laghi, L., Maggioni, M., Opocher, E., Borzio, M. and Coggi, G. (2000) Fractional allelic loss in non-end-stage cirrhosis: correlations with hepatocellular carcinoma development during follow-up. Hepatology 31, 846-850 https://doi.org/10.1053/he.2000.5790
  20. Suh, Y. J., Yang, M. H., Yoon, S. J. and Park, J. H. (2006) GEDA: new knowledge base of gene expression in drug addiction. J. Biochem. Mol. Biol. 39, 441-447 https://doi.org/10.5483/BMBRep.2006.39.4.441
  21. Teng, H., Zhang, W. Y. and Zhu, F. Q. (1994) A study on the serum pregnancy zone protein levels in pregnant women and patients with gynecological tumors. Chin. Med. J. (Engl) 107, 910-914.
  22. Xu, X. R., Huang, J., Xu, Z. G., Qian, B. Z., Zhu, Z. D., Yan, Q., Cai, T., Zhang, X., Xiao, H. S., Qu, J., Liu, F., Huang, Q. H., Cheng, Z. H., Li, N. G., Du, J. J., Hu, W., Shen, K. T., Lu, G., Fu, G., Zhong, M., Xu, S. H., Gu, W. Y., Huang, W., Zhao, X. T., Hu, G. X., Gu, J. R., Chen, Z. and Han, Z. G. (2001) Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver. Proc. Natl. Acad. Sci. USA 98, 15089-15094.Ā쁏?⨀Ā쁏?⨀ࠀࠀ椀대梖?⨀側ఀ܀롋좩Ā쁏?⨀Ā쁏?⨀椀대?⨀側ఀ܀녋좩Ā쁏?⨀Ā쁏?⨀椀대増?⨀側䐀Ā끋좩Ā쁏?⨀Ā쁏?⨀넀댐삗?⨀᝱炘?⨀顨?⨀̀̀耀 ㌀᝱碘?⨀ႝ?⨀ĀᘀԀ킜?⨀ఀ Ԁ袠?⨀Ȁ᠀Ԁ餂돀颐?⨀怙?⨀怙?⨀／ࠀ?⨀섁덀쀁?⨀耂Ѐ歸猠桥慰ｿｿｿｿ頀낙?⨀낙?⨀᠁좙?⨀좙?⨀᠂?⨀?⨀᠄?⨀?⨀?⨀耂Іဎ歸猠晲慭攠桥慰ｿｿｿｿꀁ肚?⨀肚?⨀ 颚?⨀颚?⨀ 낚?⨀낚?⨀‐좚?⨀좚?⨀䤀돀 https://doi.org/10.1073/pnas.241522398

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