Study on the activity of the signaling pathways regulating hepatocytes from G0 phase into G1 phase during rat liver regeneration

• Autorzy: Li M. , Zhou X. , Mei J. , Geng X. , Zhou Y. , Zhang W. , Xu C.
• Języki publikacji: EN

Abstrakty

EN

Under normal physiological conditions, the majority of hepatocytes are in the functional state (G0 phase). After injury or liver partial hepatectomy (PH), hepatocytes are rapidly activated to divide. To understand the mechanism underlying hepatocyte G0/G1 transition during rat liver regeneration, we used the Rat Genome 230 2.0 Array to determine the expression changes of genes, then searched the GO and NCBI databases for genes associated with the G0/G1 transition, and QIAGEN and KEGG databases for the G0/G1 transition signaling pathways. We used expression profile function (E t ) to calculate the activity level of the known G0/G1 transition signal pathways, and Ingenuity Pathway Analysis 9.0 (IPA) to determine the interactions among these signaling pathways. The results of our study show that the activity of the signaling pathways of HGF, IL-10 mediated by p38MAPK, IL-6 mediated by STAT3, and JAK/STAT mediated by Ras/ERK and STAT3 are significantly increased during the priming phase (2–6 h after PH) of rat liver regeneration. This leads us to conclude that during rat liver regeneration, the HGF, IL-10, IL-6 and JAK/STAT signaling pathways play a major role in promoting hepatocyte G0/G1 transition in the regenerating liver.

Słowa kluczowe

EN

signalling pathway; hepatocyte; G0 phase; G1 phase; rat; liver regeneration; signal transduction

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2014
• Tom: 19
• Numer: 2
• Opis fizyczny: p.181-200,fig.,ref.

Twórcy

autor

Li M.

• College of Life Science, Henan Normal University, Xinxiang 453007, P.R.China
• Key Laboratory for Cell Differentiation Regulation, Xinxiang 453007, P.R.China

autor

Zhou X.

• College of Life Science, Henan Normal University, Xinxiang 453007, P.R.China
• Key Laboratory for Cell Differentiation Regulation, Xinxiang 453007, P.R.China

autor

Mei J.

• College of Life Science, Henan Normal University, Xinxiang 453007, P.R.China
• Key Laboratory for Cell Differentiation Regulation, Xinxiang 453007, P.R.China

autor

Geng X.

• College of Life Science, Henan Normal University, Xinxiang 453007, P.R.China
• Key Laboratory for Cell Differentiation Regulation, Xinxiang 453007, P.R.China

autor

Zhou Y.

• College of Life Science, Henan Normal University, Xinxiang 453007, P.R.China
• Key Laboratory for Cell Differentiation Regulation, Xinxiang 453007, P.R.China

autor

Zhang W.

• Key Laboratory for Cell Differentiation Regulation, Xinxiang 453007, P.R.China

autor

Xu C.

• College of Life Science, Henan Normal University, Xinxiang 453007, P.R.China
• Key Laboratory for Cell Differentiation Regulation, Xinxiang 453007, P.R.China

Bibliografia

• 1. Yokoyama, Y., Nagino, M. and Nimura, Y. Mechanisms of hepatic regeneration following portal vein embolization and partial hepatectomy: a review. World J. Surg. 31 (2007) 367–374.
• 2. Vondran, F.W., Katenz, E., Schwartlander, R., Morgul, R.S., Haluk, M., Raschzok, N., Gong, X.B., Cheng, X.D., Kehr, D. and Sauer, I.M. Isolation of primary human hepatocytes after partial hepatectomy: criteria for identification of the most promising liver specimen. Artif. Organs 32 (2008) 205–213.
• 3. Estes, M.D., Do J. and Ahn, C.H. On chip cell separator using magnetic bead-based enrichment and depletion of various surface markers. Biomed. Microdevices 11 (2009) 509–515.
• 4. Michalopoulos, G.K. Liver regeneration. J. Cell Physiol. 213 (2007) 286–300.
• 5. Kountouras, J., Boura, P. and Lygidakis, N.J. Liver regeneration after hepatectomy. Hepatogastroenterology 48 (2001) 556–562.
• 6. Sell, S. The hepatocyte: heperogeneity and plasticity of liver cells. Int. J. Biochem. Cell Biol. 35 (2003) 267–271.
• 7. Zimmermann, A. Regulation of liver regeneration. Nephrol. Dial. Transplant. 19 (2004) iv6–iv10.
• 8. Fausto, N., Laird, A.D. and Webber, E.M. Liver regeneration. 2. Role of growth factors and cytokines in hepatic regeneration. FASEB J. 9 (1995) 1527–1536.
• 9. Cantz, T., Manns, M.P. and Ott, M. Stem cells in liver regeneration and therapy. Cell Tissue Res. 331 (2008) 271–282.
• 10. Xu, C.S., Chen, X.G., Chang, C.F., Wang, G.P., Wang, W.B., Zhang, L.X., Zhu, Q.S., Wang, L. and Zhang, F.C. Transcriptional profiles of biliary epithelial cells from rat regenerating liver after partial hepatectomy. Genes Genomics 34 (2012) 245–256.
• 11. Xu, C.S., Yang, Y.J., Yang, J.Y., Chen, X.G. and Wang, G.P. Analysis of the role of the integrin signaling pathway in hepatocytes during rat liver regeneration. Cell. Mol. Biol. Lett. 17 (2012) 274–288.
• 12. Michalopeulos, G.K. Liver regeneration. J. Cell Physiol. 213 (2007) 286–300.
• 13. Gómez-Lechón, M.J., Guillén, I., Ponsoda, X., Fabra, R., Trullenque, R., Nakamura, T., and Castell, J.V. Cell cycle progression proteins (cyclins), oncogene expression, and signal transduction during the proliferative response of human hepatocytes to hepatocyte growth factor. Hepatology 23 (1996) 1012–1019.
• 14. Morello, D., Fitzgerald, M.J., Babinet, C. and Fausto, N. C-myc, c-fos and c-jun regulation in the regeneration livers of normal and H-2K/c-myc transgenic mice. Mol. Cell Biol. 10 (1990) 3185–3193.
• 15. Akira, S., Isshiki, H., Sugita, T., Tanabe, O., Kinoshita, S., Nishio, Y., Nakajima, T., Hirano, T. and Kishimoto, T. A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J. 9 (1990) 1897–1906.
• 16. Zhong, Z., Wen, Z. and Darnell, J.E. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 264 (1994) 95–98.
• 17. Trautwein, C., Caelles, C., Vander, G.P., Hunter, T., Karin, M. and Chojkier, M. Transactivation by NF-IL6/LAP is enhanced by phosphorylation of its activation domain. Nature 364 (1993) 544–547.
• 18. Cressmann, D.E., Diamond, R.H. and Taub, R. Rapid activation of the Stat3 tran-scription complex in liver regeneration. Hepatology 21 (1995) 1443–1449.
• 19. Trautwein, C., Rakemann, T., Niehof, M., Rose-John, S. and Manns, M.P. Acute-phase response factor, increased binding, and target gene transcription during liver regeneration. Gastroenterology 110 (1996) 1854–1862.
• 20. Niehof, M., Manns, M.P. and Trautwein, C. CREB controls LAP/C/EBP beta transcription. Mol. Cell Biol. 17 (1997) 3600–3613.
• 21. Fujiyoshi, M. and Ozaki, M. Molecular mechanisms of liver regeneration and protection for treatment of liver dysfunction and diseases. J. Hepatobiliary Pancreat. Sci. 18 (2011) 13–22.
• 22. Higgins, G.M. and Anderson, R.M. Experimental pathology of the liver: Restoration of the liver of the white rat following partial surgical removal. Arch. Pathol. 12 (1931) 186–202.
• 23. Grisham, J.W. Cell types in rat liver cultures: their identification and isolation. Mol. Cell Biochem. 54 (1983) 23–33.
• 24. Wang, W.B., Xie, L.F., Wang, W., Wang, L. and Xu C.S. Isolation, purity and identification of hepatocytes in rat normal liver and regenerating liver. Henan Sci. 26 (2008) 1492–1498.
• 25. Strober, W. Trypan blue exclusion test of cell viability. Curr. Protoc. Immunol. 2001 May Appendix 3: Appendix 3B.
• 26. Twigger, S.N., Smith J., Zuniga-Meyer, A. and Bromberg, S.K. Exploring phenotypic data at the rat genome database. Curr. Protoc. Bioinformatics (2006) Chapter 1, Unit 1.14.
• 27. Wang, J.Z., Du, Z., Payattakool, R., Yu, P.S. and Chen, C.F. A new method to measure the semantic similarity of GO terms. Bioinformatics 23 (2007) 1274–1281.
• 28. Guo, W., Cai, C., Wang, C., Zhao, L., Wang, L. and Zhang, T. A preliminary analysis of genome structure and composition in Gossypium hirsutum. BMC Genomics 9 (2008) 314.
• 29. Xu, C.S., Wang, G.P., Zhang, L.X., Chang, C.F., Zhi, J. and Hao, Y.P. Correlation between liver cancer occurrence and gene expression profiles in rat liver tissue. Genet. Mol. Res. 10 (2011) 3480–3513.
• 30. Jiang, C., Xuan, Z., Zhao, F. and Zhang, M.Q. TRED: a transcriptional regulatory element database, new entries and other development. Nucleic Acids Res. 35 (2007) 137–140.
• 31. Childress, P.J., Flepcher, R.L. and Perumal, N.B. LymphTF-DB: a database of transcription factors involved in lymphocyte development. Genes Immun. 8 (2007) 360–365.
• 32. Wang, G.P. and Xu, C.S. Reference gene selection for real-time RT-PCR in eight kinds of rat regenerating hepatic cells. Mol. Biotechnol. 46 (2010) 49–57.
• 33. Kost, D.P. and Michalpopulos, G.K. Effect of epidermal growth factor on the expression of protooncogenes c-myc and c-Ha-ras in short-term primary hepatocyte culture. J. Cell. Physiol. 144 (1990) 122–127.
• 34. Borowiak, M., Garratt, A.N., Wustefeld, T., Strehle, M., Trautwein, C. and Birchmeier, C. Met provides essential signals for liver regeneration. Proc. Natl. Acad. Sci.USA 101 (2004) 10608–10613.
• 35. Okano, J., Shiota, G., Matsumoto, K., Yasui, S., Kurimasa, A., Hisatome, I. Steinbergd, P. and Murawakia, Y. Hepatocyte growth factor exerts a proliferative effect on oval cells through the PI3K/AKT signaling pathway. Biochem. Biophys. Res. Commun. 309 (2003) 298–304.
• 36. Stolz, D.B.，Mars, W.M., Petersen, B.E., Kim, T.H. and Michalopoulos, G.K. Growth factor signal transduction immediately after two-thirds partial hepatectomy in the rat. Cancers Res. 59 (1999) 3954–3960.
• 37. Boccaccio, C., Ando, M., Tamagnone, L., Bardelli, A., Michieli, P., Battistini, C. and Comoglio, P.M. Induction of epithelial tubules by growth factor HGF depends on the STAT pathway. Nature 391 (1998) 285–288.
• 38. Zhang, Y.W., Wang, L.M., Jove, R. and Van de Woude, G.F. Requirement of Stat3 signaling for HGF/SF-Met mediated tumorigenesis. Oncogene 21 (2002) 217–226.
• 39. Hirano, T. Interleukin 6 and its receptor: Ten years later. Int. Rev. Immunol. 16 (1998) 249-284.
• 40. Lutticken, C., Wegenka, U.M., Yuan, J., Buschmann, J., Schindler, C., Ziemiecki, A., Harpur, A.G., Wilks, A.F., Yasukawa, K., Taga, T., Kishimoto, T., Barbieri, G., Sendtner, M., Pellegrini, S., Heinrich, C. P. and Horn, F. Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signaltransducer gp130. Science 263 (1994) 89–92.
• 41. Stahl, N., Boulton, T.G., Farruggella, T., Ip. N.Y., Davis, S., Witthuhn, B.A., Quelle, F.W., Silvennoinen, O., Barbieri, G., Pellegrini, S., Ihle, J.N. and Yancopoulos, G.D. Association and activation of Jak Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components. Science 263 (1994) 92–95.
• 42. Gerhartz, C., Heesel, B., Sasse, J., Hemmann, U., Landgraf, C., SchneiderMergener, J., Horn, F., Heinrich, P.C. and Graeve, L. Differential activation of acute phase response factor/STAT3 and STAT1 via the cytoplasmic domain of the interleukin 6 signal transducer gp130. I. Definition of a novel phosphotyrosine motif mediating STAT1 activation. J. Biol. Chem. 271 (1996) 12991–12998.
• 43. Streetz, K.L., Luedde, T., Manns, M.P. and Trautwein, C. Interleukin 6 and liver regeneration. Gut 47 (2000) 309–312.
• 44. Marshall, C. J. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80 (1995) 179–185.
• 45. Cohen, C.B., Ren, R. and Baltimore, D. Modular binding domains in signal transduction proteins. Cell 80 (1995) 237–248.
• 46. Hunter, T. Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell 80 (1995) 225–236.
• 47. Heldin, C.H. Dimerization of cell surface receptors in signal transduction. Cell 80 (1995) 213–224.
• 48. Hill, C.S. and Treisman, R. Transcriptional regulation by extracellular signals: mechanisms and specificity. Cell 80 (1995) 199–212.