- Department of Liver Surgery, Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;
Objective To review the regulation of liver regeneration factors. Methods The literatures about liver regeneration related regulators in recent years were reviewed. Results With further advancement of researches on regulators of liver regeneration in recent years, there were more therapies for treatment of liver-related diseases. Regulators play important roles in the process of liver regeneration, as one of which, cell growth factor plays an essential role in liver cell proliferation, such as the proper expression of TNF-α and IL-6 promoting liver cell proliferation, HGF, TGF-α, EGF, ALR, FS, and others motivating liver cell proliferation, while TGF-β and IL-1 physically terminating liver cell proliferation. Conclusion By strengthening the studies on liver regeneration regulators, new methods may appear for treating liver-related diseases.
Citation： HUANG Xinli,WANG Xuehao. Liver Regeneration and Its Regulators. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(6): 633-638. doi: Copy
| 1. | Fausto N. Liver regeneration [J]. J Hepatol， 2000； 32（Suppl 1）: 19-31. |
| 2. | Albrecht JH, Hansen LK. Cyclin D1 promotes mitogen-independent cell cycle progression in hepatocytes [J]. Cell Growth Differ, 1999; 10(6): 397-404. |
| 3. | Trautwein C, Rakeman T, Kniehof M, et al. Acute-phase response factor, increased binding, and target gene transcription during liver regeneration [J]. Gastroenterology, 1996; 110(6): 1854-1862. |
| 4. | Fausto N. Hepatic regeneration [A]. In: Zakim D, Boyer TD. Hepatology: A Textbook of Liver Disease [M]. Philadelphia: WB Saunders， 1996: 32-38. |
| 5. | Sandgren EP, Palmiter RD, Heckel JL, et al. Complete hepatic regeneration after somatic deletion of an albumin-plasminogen activator transgene [J]. Cell, 1991; 66(2): 245-256. |
| 6. | Rhim JA, Sandgren EP, Degen JL, et al. Replacement of diseased mouse liver by hepatic cell transplantation [J]. Science, 1994; 263(5150): 1149-1152. |
| 7. | Rhim JA, Sandgren EP, Palmiter RD, et al. Complete reconstitution of mouse liver with xenogeneic hepatocytes [J]. Proc Natl Acad Sci USA, 1995; 92(11): 4942-4946. |
| 8. | Overturf K, al-Dhalimy M, Ou CN, et al. Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes [J]. Am J Pathol, 1997; 151(5): 1273-1280. |
| 9. | Higgins GM, Anderson RM. Experimental Pathology of the Liver. I. Restoration of the liver of the white rat following partial surgical removal [J]. Arch Pathol, 1931; 12: 186-202. |
| 10. | Michalopoulos GK. Liver regeneration [J]. J Cell Physiol, 2007； 213(2): 286-300. |
| 11. | LaBrecque DR, Pesch LA. Preparation and partial characterization of hepatic regenerative stimulator substance (SS) from rat liver [J]. J Physiol, 1975; 248(2): 273-284. |
| 12. | LaBrecque DR, Bachur NR. Hepatic stimulator substance: physicochemical characteristics and specificity [J]. Am J Physiol Gastrointest Liver Physiol, 1982; 242: G281-G288. |
| 13. | Francavilla A, Ove P, Polimeno L, et al. Extraction and partial purification of a hepatic stimulatory substance in rats, mice, and dogs [J]. Cancer Research, 1987; 47（21）: 5600-5605. |
| 14. | Hagiya M, Francarilla A, Polimeno L, et al. Cloning and sequence analysis of the rat augmenter of liver regeneration (ALR) gene: expression of biologically active recombination ALR and demonstration of tissue distribution [J]. Proc Natl Acad Sci USA, 1994; 91（17）: 8142-8146. |
| 15. | Giorda R, Hagiya M, Seki T, et al. Analysis of the structure and expression of the augmenter of liver regeneration (ALR) gene [J]. Molecular Medicine, 1996; 2（1）: 97-108. |
| 16. | Francavilla A, Hagiya M, Porter KA, et al. Augmenter of liver regeneration: its place in the universe of hepatic growth factors [J]. Hepatology, 1994; 20（3）: 747-757. |
| 17. | Wang CP, Zhou L, Su SH, et al. Augmenter of liver regeneration promotes hepatocyte proliferation induced by Kupffer cells [J]. World J Gastroenterol, 2006, 12(30): 4859-4865. |
| 18. | Francavilla A, Vujanovic NL, Polimeno L, et al. The in vivo effect of hepatotrophic factors augmenter of liver regeneration, hepatocyte growth factor, and insulin-like growth factor on liver natural killer cell functions [J]. Hepatology, 1997; 25(2): 411-415. |
| 19. | Thasler WE, Dayoub R, Mühlbauer M, et al. Repression of cytochrome P450 activity in human hepatocytes in vitro by a novel hepatotrophic factor, augmenter of liver regeneration [J]. J Pharmacol Exp Ther, 2006; 316(2): 822-849. |
| 20. | Nakamura T, Takio K, Eto Y, et al. Activin-binding protein from rat ovary is follistatin [J]. Science, 1990; 247(4944): 836-838. |
| 21. | Hully JR, Chang L, Schwall RH, et al. Induction of apoptosis in the murine liver with recombinant human activin A [J]. Hepatology, 1994; 20(4 pt 1): 854-862. |
| 22. | Yasuda H, Mine T, Shibata H, et al. Activin A: An autocrine inhibitor of initiation of DNA synthesis in rat hepatocytes [J]. J Clin Invest, 1993; 92(3): 1491-1496. |
| 23. | Schwall RH, Robbins K, Jardieu P, et al. Activin induces cell death in hepatocytes in vivo and in vitro [J]. Hepatology, 1993; 18(2): 347-356. |
| 24. | Takehara-Kasamatsu Y, Tsuchida K, Nakatani M, et al. Characterization of follistatin-related gene as a negative regulatory factor for actvin family members duringmouse heart development [J]. J Med Invest, 2007; 54(3-4): 276-288. |
| 25. | Zhang YQ, Kanzaki M, Shibata H, et al. Regulation of the expression of follistatin in rat hepatocytes [J]. Biochim Biophys Acta, 1997; 1354(3): 204-210. |
| 26. | Kogure K, Zhang YQ, Kanzaki M, et al. Intravenous administration of follistatin: delivery to the liver and effect on liver regeneration after partial hepatectomy [J]. Hepatology, 1996; 24(2): 361-366. |
| 27. | Kogure K, Omata W, Kanzaki M, et al. A single intraportal administration of follistatin accelerates liver regeneration in partially hepatectomized rats[J]. Gastroenterology, 1995; 108(4): 1136-1142. |
| 28. | Kogure K, Zhang YQ, Shibata H, et al. Immediate onset of DNA synthesis in remnant rat liver after 90% hepatectomy by an administration of follistatin[J]. J Hepatol, 1998; 29(6): 977-984. |
| 29. | Ishiki Y, Ohnishi H, Muto Y, et al. Direct evidence that hepatocyte growth factor is a hepatotrophic factor for liver regeneration and has a potent antihepatitis effect in vivo [J]. Hepatology, 1992; 16(5): 1227-1235. |
| 30. | Huh CG, Factor VM, Sánchez A, et al. Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair[J]. Proc Natl Acad Sci USA, 2004; 101(13): 4477-4482. |
| 31. | Taub R. Liver regeneration: from myth to mechanism [J]. Nat Rev Mol Cell Biol, 2004; 5(10): 836-847. |
| 32. | Lindroos PM, Zarnegar R, Michalopoulos GK. Hepatocyte growth factor (hepatopoietin A) rapidly increases in plasma before DNA synthesis and liver regeneration stimulated by partial hepatectomy and carbon tetrachloride administration [J]. Hepatology, 1991; 13(4): 743-749. |
| 33. | Michalopoulos GK, Defrances MC. Liver regeneration [J]. Science, 1997; 276(5309): 60-66. |
| 34. | Michalopoulos GK, Zarnegav R. Hepatocyte growth factor [J]. Hepatology, 1992; 151(1): 149-155. |
| 35. | Masson S, Daveau M, Hiron M. Differential regeneration response and expression of growth factors following hepatectomy of variable extent in rats [J]. Liver, 1999; 19(4): 312-317. |
| 36. | Kaido T, Yoshikawa A, Seto S. Hepatocyte growth factor supply accelerates compensatory hypertrophy caused by portal branch ligation in normal and jaundiced rats [J]. J Surg Res, 1999; 85(1): 115-119. |
| 37. | Shiota G, Kawasaki H. Hepatocyte growth factor in transgenic mice [J]. Int J Exp Pathol, 1998; 79(5): 267-277. |
| 38. | Assy N, Minuk GY. Liver regeneration: methods for monitoring and their applications [J]. J Hepatol, 1997; 26（4）: 945-952. |
| 39. | Rai RM, Loffreda S, Karp CL. Kupffer cell depletion abolishes induction of interleukin-10 and permits sustained overexpression of tumor necrosis factor alpha messenger RNA in the regenerating rat liver[J]. Hepatology, 1997; 25（4）: 889-895. |
| 40. | Boulton R, Woodman A, Calnan D. Nonparenchymal cells from regenerating rat liver generate interleukin-1alpha and -1beta: a mechanism of negative regulation of hepatocyte proliferation.[J]. Hepatology, 1997; 26(1): 49-58. |
| 41. | Mangnall D, Bird NC, Majeed AW, et al. The molecular physiology of liver regeneration following patial hepatectomy [J]. Liver Int, 2003; 23(2): 124-138. |
| 42. | Fausto N, Riehle KJ. Mechanisms of liver regeneration and their clinical implications[J]. J Hepatobiliary Pancreat Surg, 2005; 12(3): 181-189. |
| 43. | Fausto N, Campbell JS, Riehle KJ. Liver regeneration [J]. Hepatology, 2006; 43(2 Suppl 1): S45-S53. |
| 44. | Cressman DE, Greenbaum LE, DeAngelis RA, et al. Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice [J]. Science, 1996; 274(5291): 1379-1383. |
| 45. | Ohira H, Miyata M, Kuroda M, et al. Interleukin-6 induces proliferation of rat hepatocytes in vivo [J]. J Hepatol, 1996; 25(6): 941-947. |
| 46. | Boulton RA, Alison MR, Golding M, et al. Augmentation of the early phase of liver regeneration after 70% partial hepatectomy in rats following selective Kupffer cell depletion [J]. J Hepatology, 1998; 29(2): 271-280. |
| 47. | Herrington J, Smit LS, Schwartz J, et al. The role of STAT proteins in growth hormone signaling [J]. Oncogene, 2000; 19(21): 2585-2597. |
| 48. | Roskams T, De Vos R, Van Eyken P, et al. Hepatic OV-6 expression in human liver disease and rat experiments: evidence for hepatic progenitor cells in man [J]. J Hepatol, 1998; 29(3): 455-463. |
| 49. | Vacková I, Engelová M, Marinov I， et al.Cell cycle synchronization of porcine granulosa cells in G1 stage with mimosine[J]. Anim Reprod Sci, 2003; 77(3-4)： 235-245. |
| 50. | Kiso S, Kawata S, Tamura S, et al. Liver regeneration in heparin-binding EGF-like growth factor transgenic mice after partial hepatectomy[J]. Gastroenterology, 2003; 124(3): 701-707. |
| 51. | Mitchell C, Nivison M, Jackson LF, et al． Heparin-binding epidermal growth factor-like growth factor links hepatocyte priming with cell cycle progression during liver regeneration[J]. J Biol Chem， 2005; 280(4): 2562-2568. |
| 52. | Webber EM, Bruix J, Pierce RH, et al. Tumor necrosis factor primes hepatocytes for DNA replication in the rat [J]. Hepatology, 1998; 28(5): 1226-1234. |
| 53. | Peng Y, Du K, Ramirez S, et al. Mitogenic up-regulation of the PRL-1 protein-tyrosine phosatatse gene by Egr-1. Egr-1 activation is an event in liver regeneration [J]. J Biol Chem, 1999; 274(8): 4513-4520. |
| 54. | Sell S. Comparison of liver progenitor cells in human atypical ductular reactions with those seen in experimental models of liver injury [J]. Hepatology, 1998; 27(2): 317-331. |
| 55. | Gallucci RM, Simeonova PP, Toriumi W, et al. TNF-alpha regulates transforming growth factor-alpha expression in regenerating murine liver and isolated hepatocytes [J]. J Immunol, 2000; 164(2): 872-878. |
| 56. | Wullaert A, van Loo G, Heyninck K, et al．Hepatic tumor necrosis factor signaling and nuclear factor-kappaB： effects on liver homeostasis and beyond [J]. Endocr Rev, 2007; 28(4): 365-386. |
| 57. | Sánchez A, Factor VM, Schroeder IS, et al. Activation of NF-kappaB and STAT3 in rat oval cells during 2-acetylaminofluorene／partial hepatectomy-induced liver regeneration [J]. Hepatology, 2004; 39(2): 376-385. |
| 58. | Akhurst B, Matthews V, Husk K, et al. Differential lymphotoxin-beta and interferon gamma signaling duringmouse liver regeneration induced by chronic and acute injury [J]. Hepatology, 2005; 41(2): 327-335. |
| 59. | Zhang JY, Adams AE, Ridky TW, et al. Tumor necrosis factor receptor l／c-Jun-NH2-kinase signaling promotes human neoplasia [J]. Cancer Res, 2007; 67(8): 3827-3834. |
| 60. | Tesz GJ, Guilheme A, Guntur KV, et al. Tumor necrosis factor alpha (TNFalpha) stimulates Map4k4 expression through TNFalpha receptor 1 signaling to c-Jun and activating transcription factor 2 [J]. J Biol Chem, 2007; 282(27): 19302-19312. |
| 61. | Pardoux C, Asselin-Paturel C, Chehimi J, et al. Functional interaction between TGF-β and IL-12 in human primary allogeneic cytoxicity and proliferative response [J]. J Immunol, 1997; 158(1): 136-143. |
| 62. | Lee SJ, Kim YG， Kang KW， et al. Effects of colchicine on liver functions of cirrhotic rats： beneficial effects result from stellate cell in activation and inhibition of TGF betal expression [J]. Chem Biol Interact, 2004; 147(1): 9-21. |
| 63. | Oe S,Lemmer ER,Conner EA,et al. Intact signaling by transforming growth factor beta is not required for termination of liver regeneration in mice [J]. Hepatology, 2004; 40(5): 1098-1105. |
- 1. Fausto N. Liver regeneration [J]. J Hepatol， 2000； 32（Suppl 1）: 19-31.
- 2. Albrecht JH, Hansen LK. Cyclin D1 promotes mitogen-independent cell cycle progression in hepatocytes [J]. Cell Growth Differ, 1999; 10(6): 397-404.
- 3. Trautwein C, Rakeman T, Kniehof M, et al. Acute-phase response factor, increased binding, and target gene transcription during liver regeneration [J]. Gastroenterology, 1996; 110(6): 1854-1862.
- 4. Fausto N. Hepatic regeneration [A]. In: Zakim D, Boyer TD. Hepatology: A Textbook of Liver Disease [M]. Philadelphia: WB Saunders， 1996: 32-38.
- 5. Sandgren EP, Palmiter RD, Heckel JL, et al. Complete hepatic regeneration after somatic deletion of an albumin-plasminogen activator transgene [J]. Cell, 1991; 66(2): 245-256.
- 6. Rhim JA, Sandgren EP, Degen JL, et al. Replacement of diseased mouse liver by hepatic cell transplantation [J]. Science, 1994; 263(5150): 1149-1152.
- 7. Rhim JA, Sandgren EP, Palmiter RD, et al. Complete reconstitution of mouse liver with xenogeneic hepatocytes [J]. Proc Natl Acad Sci USA, 1995; 92(11): 4942-4946.
- 8. Overturf K, al-Dhalimy M, Ou CN, et al. Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes [J]. Am J Pathol, 1997; 151(5): 1273-1280.
- 9. Higgins GM, Anderson RM. Experimental Pathology of the Liver. I. Restoration of the liver of the white rat following partial surgical removal [J]. Arch Pathol, 1931; 12: 186-202.
- 10. Michalopoulos GK. Liver regeneration [J]. J Cell Physiol, 2007； 213(2): 286-300.
- 11. LaBrecque DR, Pesch LA. Preparation and partial characterization of hepatic regenerative stimulator substance (SS) from rat liver [J]. J Physiol, 1975; 248(2): 273-284.
- 12. LaBrecque DR, Bachur NR. Hepatic stimulator substance: physicochemical characteristics and specificity [J]. Am J Physiol Gastrointest Liver Physiol, 1982; 242: G281-G288.
- 13. Francavilla A, Ove P, Polimeno L, et al. Extraction and partial purification of a hepatic stimulatory substance in rats, mice, and dogs [J]. Cancer Research, 1987; 47（21）: 5600-5605.
- 14. Hagiya M, Francarilla A, Polimeno L, et al. Cloning and sequence analysis of the rat augmenter of liver regeneration (ALR) gene: expression of biologically active recombination ALR and demonstration of tissue distribution [J]. Proc Natl Acad Sci USA, 1994; 91（17）: 8142-8146.
- 15. Giorda R, Hagiya M, Seki T, et al. Analysis of the structure and expression of the augmenter of liver regeneration (ALR) gene [J]. Molecular Medicine, 1996; 2（1）: 97-108.
- 16. Francavilla A, Hagiya M, Porter KA, et al. Augmenter of liver regeneration: its place in the universe of hepatic growth factors [J]. Hepatology, 1994; 20（3）: 747-757.
- 17. Wang CP, Zhou L, Su SH, et al. Augmenter of liver regeneration promotes hepatocyte proliferation induced by Kupffer cells [J]. World J Gastroenterol, 2006, 12(30): 4859-4865.
- 18. Francavilla A, Vujanovic NL, Polimeno L, et al. The in vivo effect of hepatotrophic factors augmenter of liver regeneration, hepatocyte growth factor, and insulin-like growth factor on liver natural killer cell functions [J]. Hepatology, 1997; 25(2): 411-415.
- 19. Thasler WE, Dayoub R, Mühlbauer M, et al. Repression of cytochrome P450 activity in human hepatocytes in vitro by a novel hepatotrophic factor, augmenter of liver regeneration [J]. J Pharmacol Exp Ther, 2006; 316(2): 822-849.
- 20. Nakamura T, Takio K, Eto Y, et al. Activin-binding protein from rat ovary is follistatin [J]. Science, 1990; 247(4944): 836-838.
- 21. Hully JR, Chang L, Schwall RH, et al. Induction of apoptosis in the murine liver with recombinant human activin A [J]. Hepatology, 1994; 20(4 pt 1): 854-862.
- 22. Yasuda H, Mine T, Shibata H, et al. Activin A: An autocrine inhibitor of initiation of DNA synthesis in rat hepatocytes [J]. J Clin Invest, 1993; 92(3): 1491-1496.
- 23. Schwall RH, Robbins K, Jardieu P, et al. Activin induces cell death in hepatocytes in vivo and in vitro [J]. Hepatology, 1993; 18(2): 347-356.
- 24. Takehara-Kasamatsu Y, Tsuchida K, Nakatani M, et al. Characterization of follistatin-related gene as a negative regulatory factor for actvin family members duringmouse heart development [J]. J Med Invest, 2007; 54(3-4): 276-288.
- 25. Zhang YQ, Kanzaki M, Shibata H, et al. Regulation of the expression of follistatin in rat hepatocytes [J]. Biochim Biophys Acta, 1997; 1354(3): 204-210.
- 26. Kogure K, Zhang YQ, Kanzaki M, et al. Intravenous administration of follistatin: delivery to the liver and effect on liver regeneration after partial hepatectomy [J]. Hepatology, 1996; 24(2): 361-366.
- 27. Kogure K, Omata W, Kanzaki M, et al. A single intraportal administration of follistatin accelerates liver regeneration in partially hepatectomized rats[J]. Gastroenterology, 1995; 108(4): 1136-1142.
- 28. Kogure K, Zhang YQ, Shibata H, et al. Immediate onset of DNA synthesis in remnant rat liver after 90% hepatectomy by an administration of follistatin[J]. J Hepatol, 1998; 29(6): 977-984.
- 29. Ishiki Y, Ohnishi H, Muto Y, et al. Direct evidence that hepatocyte growth factor is a hepatotrophic factor for liver regeneration and has a potent antihepatitis effect in vivo [J]. Hepatology, 1992; 16(5): 1227-1235.
- 30. Huh CG, Factor VM, Sánchez A, et al. Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair[J]. Proc Natl Acad Sci USA, 2004; 101(13): 4477-4482.
- 31. Taub R. Liver regeneration: from myth to mechanism [J]. Nat Rev Mol Cell Biol, 2004; 5(10): 836-847.
- 32. Lindroos PM, Zarnegar R, Michalopoulos GK. Hepatocyte growth factor (hepatopoietin A) rapidly increases in plasma before DNA synthesis and liver regeneration stimulated by partial hepatectomy and carbon tetrachloride administration [J]. Hepatology, 1991; 13(4): 743-749.
- 33. Michalopoulos GK, Defrances MC. Liver regeneration [J]. Science, 1997; 276(5309): 60-66.
- 34. Michalopoulos GK, Zarnegav R. Hepatocyte growth factor [J]. Hepatology, 1992; 151(1): 149-155.
- 35. Masson S, Daveau M, Hiron M. Differential regeneration response and expression of growth factors following hepatectomy of variable extent in rats [J]. Liver, 1999; 19(4): 312-317.
- 36. Kaido T, Yoshikawa A, Seto S. Hepatocyte growth factor supply accelerates compensatory hypertrophy caused by portal branch ligation in normal and jaundiced rats [J]. J Surg Res, 1999; 85(1): 115-119.
- 37. Shiota G, Kawasaki H. Hepatocyte growth factor in transgenic mice [J]. Int J Exp Pathol, 1998; 79(5): 267-277.
- 38. Assy N, Minuk GY. Liver regeneration: methods for monitoring and their applications [J]. J Hepatol, 1997; 26（4）: 945-952.
- 39. Rai RM, Loffreda S, Karp CL. Kupffer cell depletion abolishes induction of interleukin-10 and permits sustained overexpression of tumor necrosis factor alpha messenger RNA in the regenerating rat liver[J]. Hepatology, 1997; 25（4）: 889-895.
- 40. Boulton R, Woodman A, Calnan D. Nonparenchymal cells from regenerating rat liver generate interleukin-1alpha and -1beta: a mechanism of negative regulation of hepatocyte proliferation.[J]. Hepatology, 1997; 26(1): 49-58.
- 41. Mangnall D, Bird NC, Majeed AW, et al. The molecular physiology of liver regeneration following patial hepatectomy [J]. Liver Int, 2003; 23(2): 124-138.
- 42. Fausto N, Riehle KJ. Mechanisms of liver regeneration and their clinical implications[J]. J Hepatobiliary Pancreat Surg, 2005; 12(3): 181-189.
- 43. Fausto N, Campbell JS, Riehle KJ. Liver regeneration [J]. Hepatology, 2006; 43(2 Suppl 1): S45-S53.
- 44. Cressman DE, Greenbaum LE, DeAngelis RA, et al. Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice [J]. Science, 1996; 274(5291): 1379-1383.
- 45. Ohira H, Miyata M, Kuroda M, et al. Interleukin-6 induces proliferation of rat hepatocytes in vivo [J]. J Hepatol, 1996; 25(6): 941-947.
- 46. Boulton RA, Alison MR, Golding M, et al. Augmentation of the early phase of liver regeneration after 70% partial hepatectomy in rats following selective Kupffer cell depletion [J]. J Hepatology, 1998; 29(2): 271-280.
- 47. Herrington J, Smit LS, Schwartz J, et al. The role of STAT proteins in growth hormone signaling [J]. Oncogene, 2000; 19(21): 2585-2597.
- 48. Roskams T, De Vos R, Van Eyken P, et al. Hepatic OV-6 expression in human liver disease and rat experiments: evidence for hepatic progenitor cells in man [J]. J Hepatol, 1998; 29(3): 455-463.
- 49. Vacková I, Engelová M, Marinov I， et al.Cell cycle synchronization of porcine granulosa cells in G1 stage with mimosine[J]. Anim Reprod Sci, 2003; 77(3-4)： 235-245.
- 50. Kiso S, Kawata S, Tamura S, et al. Liver regeneration in heparin-binding EGF-like growth factor transgenic mice after partial hepatectomy[J]. Gastroenterology, 2003; 124(3): 701-707.
- 51. Mitchell C, Nivison M, Jackson LF, et al． Heparin-binding epidermal growth factor-like growth factor links hepatocyte priming with cell cycle progression during liver regeneration[J]. J Biol Chem， 2005; 280(4): 2562-2568.
- 52. Webber EM, Bruix J, Pierce RH, et al. Tumor necrosis factor primes hepatocytes for DNA replication in the rat [J]. Hepatology, 1998; 28(5): 1226-1234.
- 53. Peng Y, Du K, Ramirez S, et al. Mitogenic up-regulation of the PRL-1 protein-tyrosine phosatatse gene by Egr-1. Egr-1 activation is an event in liver regeneration [J]. J Biol Chem, 1999; 274(8): 4513-4520.
- 54. Sell S. Comparison of liver progenitor cells in human atypical ductular reactions with those seen in experimental models of liver injury [J]. Hepatology, 1998; 27(2): 317-331.
- 55. Gallucci RM, Simeonova PP, Toriumi W, et al. TNF-alpha regulates transforming growth factor-alpha expression in regenerating murine liver and isolated hepatocytes [J]. J Immunol, 2000; 164(2): 872-878.
- 56. Wullaert A, van Loo G, Heyninck K, et al．Hepatic tumor necrosis factor signaling and nuclear factor-kappaB： effects on liver homeostasis and beyond [J]. Endocr Rev, 2007; 28(4): 365-386.
- 57. Sánchez A, Factor VM, Schroeder IS, et al. Activation of NF-kappaB and STAT3 in rat oval cells during 2-acetylaminofluorene／partial hepatectomy-induced liver regeneration [J]. Hepatology, 2004; 39(2): 376-385.
- 58. Akhurst B, Matthews V, Husk K, et al. Differential lymphotoxin-beta and interferon gamma signaling duringmouse liver regeneration induced by chronic and acute injury [J]. Hepatology, 2005; 41(2): 327-335.
- 59. Zhang JY, Adams AE, Ridky TW, et al. Tumor necrosis factor receptor l／c-Jun-NH2-kinase signaling promotes human neoplasia [J]. Cancer Res, 2007; 67(8): 3827-3834.
- 60. Tesz GJ, Guilheme A, Guntur KV, et al. Tumor necrosis factor alpha (TNFalpha) stimulates Map4k4 expression through TNFalpha receptor 1 signaling to c-Jun and activating transcription factor 2 [J]. J Biol Chem, 2007; 282(27): 19302-19312.
- 61. Pardoux C, Asselin-Paturel C, Chehimi J, et al. Functional interaction between TGF-β and IL-12 in human primary allogeneic cytoxicity and proliferative response [J]. J Immunol, 1997; 158(1): 136-143.
- 62. Lee SJ, Kim YG， Kang KW， et al. Effects of colchicine on liver functions of cirrhotic rats： beneficial effects result from stellate cell in activation and inhibition of TGF betal expression [J]. Chem Biol Interact, 2004; 147(1): 9-21.
- 63. Oe S,Lemmer ER,Conner EA,et al. Intact signaling by transforming growth factor beta is not required for termination of liver regeneration in mice [J]. Hepatology, 2004; 40(5): 1098-1105.