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Comparative analysis of gene expression profiles of OPN signalling pathway in four kinds of liver diseases

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Abstract

To explore the relevance of OPN signalling pathway to the occurrence and development of nonalcoholic fatty liver disease (NAFLD), liver cirrhosis (LC), hepatic cancer (HC) and acute hepatic failure (AHF) at transcriptional level, Rat Genome 230 2.0 Array was used to detect expression profiles of OPN signalling pathway-related genes in four kinds of liver diseases. The results showed that 23, 33, 59 and 74 genes were significantly changed in the above four kinds of liver diseases, respectively. H-clustering analysis showed that the expression profiles of OPN signalling-related genes were notably different in four kinds of liver diseases. Subsequently, a total of above-mentioned 147 genes were categorized into four clusters by k-means according to the similarity of gene expression, and expression analysis systematic explorer (EASE) functional enrichment analysis revealed that OPN signalling pathway-related genes were involved in cell adhesion and migration, cell proliferation, apoptosis, stress and inflammatory reaction, etc. Finally, ingenuity pathway analysis (IPA) software was used to predict the functions of OPN signalling-related genes, and the results indicated that the activities of ROS production, cell adhesion and migration, cell proliferation were remarkably increased, while that of apoptosis, stress and inflammatory reaction were reduced in four kinds of liver diseases. In summary, the above physiological activities changed more obviously in LC, HC and AHF than in NAFLD.

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References

  • Behera R., Kumar V., Lohite K., Karnik S. and Kundu G. C. 2010 Activation of JAK2/STAT3 signaling by osteopontin promotes tumor growth in human breast cancer cells. Carcinogenesis 31, 192–200.

    Article  CAS  PubMed  Google Scholar 

  • Chakraborty G., Jain S., Behera R., Ahmed M., Sharma P., Kumar V. et al. 2006 The multifaceted roles of osteopontin in cell signaling, tumor progression and angiogenesis. Curr. Mol. Med. 6, 819–830.

    Article  CAS  PubMed  Google Scholar 

  • Chen L. Y., Yang B., Zhou L., Ren F., Duan Z. P. and Ma Y. J. 2015 Promotion of mitochondrial energy metabolism during hepatocyte apoptosis in a rat model of acute liver failure. Mol. Med. Rep. 12, 5035–5041.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Denhardt D. T., Giachelli C. M. and Rittling S. R. 2001 Role of osteopontin in cellular signaling and toxicant injury. Annu. Rev. Pharmacol. Toxicol. 41, 723–749.

    Article  CAS  PubMed  Google Scholar 

  • Ganji S. H., Kashyap M. L. and Kamanna V. S. 2015 Niacin inhibits fat accumulation, oxidative stress, and inflammatory cytokine IL-8 in cultured hepatocytes: impact on non-alcoholic fatty liver disease. Metabolism 64, 982–990.

    Article  CAS  PubMed  Google Scholar 

  • Guo G. B. and Xu C. S. 2008 Expression profiles of the organic acid metabolism-associated genes during rat liver regeneration. Amino Acids 34, 597–604.

    Article  CAS  PubMed  Google Scholar 

  • Hosack D. A., Dennis Jr. G., Sherman B. T., Lane H. C. and Lempicki R. A. 2003 Identifying biological themes within list of genes with EASE. Genome Biol. 4, R70.

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang L., Wei M. F. and Feng J. X. 2008 Abnormal activation of OPN inflammation pathway in livers of children with biliary atresia and relationship to hepatic fibrosis. Eur. J. Pediatr. Surg. 18, 224–229.

    Article  CAS  PubMed  Google Scholar 

  • Jiang T., Wang L., Li X., Song J., Wu X. and Zhou S. 2015 Inositol-requiring enzyme 1-mediated endoplasmic reticulum stress triggers apoptosis and fibrosis formation in liver cirrhosis rat models. Mol. Med. Rep. 11, 2941–2946.

    CAS  PubMed  Google Scholar 

  • Kiefer F. W., Zeyda M., Gollinger K., Pfau B., Neuhofer A., Weichhart T. et al. 2010 Neutralization of osteopontin inhibits obesity-induced inflammation and insulin resistance. Diabetes 59, 935–946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lai L., Yang X., Xu X., Jiang Y. and Tong M. 2005 Establishment of animal model with acute hepatic failure caused by lavage carbon tetrachloride. China J. Mod. Med. 15, 1155–1157.

    Google Scholar 

  • Lee S. H., Seo G. S., Park Y. N., Yoo T. M. and Sohn D. H. 2004 Effects and regulation of osteopontin in rat hepatic stellate cells. Biochem. Pharmacol. 68, 2367–2378.

    Article  CAS  PubMed  Google Scholar 

  • Lima-Cabello E., Garcia-Mediavilla M. V., Miquilena-Colina M. E., Vargas-Castrillon J., Lozano-Rodriguez T., Fernandez-Bermejo M. et al. 2011 Enhanced expression of pro-inflammatory mediators and liver X-receptor-regulated lipogenic genes in non-alcoholic fatty liver disease and hepatitis C. Clin. Sci. (London) 120, 239–250.

    Article  CAS  Google Scholar 

  • Liu Y. F., Zha B. S., Zhang H. L., Zhu X. J., Li Y. H., Zhu J. et al. 2009 Characteristic gene expression profiles in the progression from liver cirrhosis to carcinoma induced by diethylnitrosamine in a rat model. J. Exp. Clin. Cancer Res. 28, 107.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lin Y. H. and Yang-Yen H. F. 2001 The osteopontin-CD44 survival signal involves activation of the phosphatidylinositol 3-kinase/Akt signaling pathway. J. Biol. Chem. 276, 46024–46030.

    Article  CAS  PubMed  Google Scholar 

  • Nagoshi S. 2014 Osteopontin: versatile modulator of liver diseases. Hepatol. Res. 44, 22–30.

    Article  CAS  PubMed  Google Scholar 

  • Otu H. H., Naxerova K., Ho K., Can H., Nesbitt N., Libermann T. A. et al. 2007 Restoration of liver mass after injury requires proliferative and not embryonic transcriptional patterns. J. Biol. Chem. 282, 11197–11204.

    Article  CAS  PubMed  Google Scholar 

  • Phillips R. J., Helbig K. J., Van der Hoek K. H., Seth D. and Beard M. R. 2012 Osteopontin increases hepatocellular carcinoma cell growth in a CD44 dependant manner. World J. Gastroenterol. 18, 3389–3399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qin L. 2014 Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies. Front. Med. 8, 24–32.

    Article  PubMed  Google Scholar 

  • Sahai A., Malladi P., Melin-Aldana H., Green R. M. and Whitington P. F. 2004 Upregulation of osteopontin expression is involved in the development of nonalcoholic steatohepatitis in a dietary murine model. Am. J. Physiol. Gastrointest. Liver Physiol. 287, G264–G273.

    Article  CAS  PubMed  Google Scholar 

  • Sodek J., Ganss B. and McKee M. D. 2000 Osteopontin. Crit. Rev. Oral Biol. Med. 11, 279–303.

    Article  CAS  PubMed  Google Scholar 

  • Srungaram P., Rule J. A., Yuan H. J., Reimold A., Dahl B., Sanders C. et al. 2015 Plasma osteopontin in acute liver failure. Cytokine 73, 270–276.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun B. S., Dong Q. Z., Ye Q. H., Sun H. J., Jia H. L., Zhu X. Q. et al. 2008 Lentiviral-mediated miRNA against osteopontin suppresses tumor growth and metastasis of human hepatocellular carcinoma. Hepatology 48, 1834–1842.

    Article  CAS  PubMed  Google Scholar 

  • Tajiri T., Tate G., Kunimura T., Endo Y., Inoue K., Mitsuya T. et al. 2005 Osteopontin expression in proliferated bile ductules: the correlation with liver damage in fulminant hepatitis. Dig. Dis. Sci. 50, 188–195.

    Article  CAS  PubMed  Google Scholar 

  • Tiwari A., Shivananda S., Gopinath K. S. and Kumar A. 2014 MicroRNA-125a reduces proliferation and invasion of oral squamous cell carcinoma cells by targeting estrogen-related receptor alpha: implications for cancer therapeutics. J. Biol. Chem. 289, 32276–32290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Urtasun R., Lopategi A., George J., Leung T. M., Lu Y., Wang X. et al. 2012 Osteopontin, an oxidant stress sensitive cytokine, up-regulates collagen-I via integrin alpha(V)beta(3) engagement and PI3K/pAkt/NFkappaB signaling. Hepatology 55, 594–608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang G., Li X., Chen S., Zhao W., Yang J., Chang C. et al. 2015 Expression profiles uncover the correlation of OPN signaling pathways with rat liver regeneration at cellular level. Cell Biol. Int. 39, 1329–1340.

    Article  CAS  PubMed  Google Scholar 

  • Wang G. P. and Xu C. S. 2010a Reference gene selection for real-time RT-PCR in eight kinds of rat regenerating hepatic cells. Mol. Biotechnol. 46, 49–57.

    Article  PubMed  Google Scholar 

  • Wang G. P. and Xu C. S. 2010b Roles of osteopontin in liver development, regeneration and liver diseases. Chem. Life 30, 464–468.

    Google Scholar 

  • Wang K. X. and Denhardt D. T. 2008 Osteopontin: role in immune regulation and stress responses. Cytokine Growth Factor Rev. 19, 333–345.

    Article  CAS  PubMed  Google Scholar 

  • Wang X., Lopategi A., Ge X., Lu Y., Kitamura N., Urtasun R. et al. 2014 Osteopontin induces ductular reaction contributing to liver fibrosis. Gut 63, 1805–1818.

    Article  CAS  PubMed  Google Scholar 

  • Wu X. L., Lin K. J., Bai A. P., Wang W. X., Meng X. K., Su X. L. et al. 2014 Osteopontin knockdown suppresses the growth and angiogenesis of colon cancer cells. World J. Gastroenterol. 20, 10440–10448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu Y., Jiang W., Wang Y., Wu J., Saiyin H., Qiao X. et al. 2012 Breast cancer metastasis suppressor 1 regulates hepatocellular carcinoma cell apoptosis via suppressing osteopontin expression. PLoS One 7, e42976.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu C., Wang G., Hao Y., Zhi J., Zhang L. and Chang C. 2011a Correlation analysis between gene expression profile of rat liver tissues and high-fat emulsion-induced nonalcoholic fatty liver. Dig. Dis. Sci. 56, 2299–2308.

    Article  CAS  PubMed  Google Scholar 

  • Xu C. S., Wang G. P., Zhang L. X., Chang C. F., Zhi J. and Hao Y. P. 2011b Correlation between liver cancer occurrence and gene expression profiles in rat liver tissue. Genet. Mol. Res. 10, 3480–3513.

    Article  CAS  PubMed  Google Scholar 

  • Yang H., Guo H., Fan K., Zhang B., Zhao L., Hou S. et al. 2011 Clearance of propionibacterium acnes by kupffer cells is regulated by osteopontin through modulating the expression of p47phox. Mol. Immunol. 48, 2019–2026.

    Article  CAS  PubMed  Google Scholar 

  • Zhao J., Dong L., Lu B., Wu G., Xu D., Chen J. et al. 2008 Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis. Gastroenterology 135, 956–968.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was funded by the National Natural Science Foundation Project of China (no. 81200317), the Natural Science Foundation of China (no. 31572270), the Major Scientific and Technological Projects of Henan (no. 111100910600), the doctoral Scientific Research Start-up Foundation of Henan Normal University (no. 11128), and the Youth Science Foundation of Henan Normal University (no. 2013qk12). We thank Mr Yunpeng Hao and Mr Jia Zhi for their hard work in preparing animal models, Dr Cuifang Chang for her data analysis, and Ms Jun Li for her hard work during revising the manuscript.

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Correspondence to CUNSHUAN XU.

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[Wang G., Chen S., Zhao C., Li X., Zhao W., Yang J., Chang C. and Xu C. 2016 Comparative analysis of gene expression profiles of OPN signalling pathway in four kinds of liver diseases. J. Genet. 95, xx–xx]

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WANG, G., CHEN, S., ZHAO, C. et al. Comparative analysis of gene expression profiles of OPN signalling pathway in four kinds of liver diseases. J Genet 95, 741–750 (2016). https://doi.org/10.1007/s12041-016-0673-7

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  • DOI: https://doi.org/10.1007/s12041-016-0673-7

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