期刊论文详细信息
Cell Division
To divide or not to divide: revisiting liver regeneration
Atsushi Miyajima2  Yuichiro Miyaoka1 
[1] Current address: Gladstone Institute of Cardiovascular Disease, University of California at San Francisco, San Francisco, CA 94158, USA;Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
关键词: Polyploidy;    Partial hepatectomy;    mTOR;    Liver regeneration;    Hepatocyte;    E2F family;    Cyclins;    Cellular hypertrophy;    Cdks;    Akt;   
Others  :  790594
DOI  :  10.1186/1747-1028-8-8
 received in 2013-06-06, accepted in 2013-06-17,  发布年份 2013
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【 摘 要 】

The liver has a remarkable capacity to regenerate. Even with surgical removal (partial hepatectomy) of 70% of liver mass, the remnant tissue grows to recover the original mass and functions. Liver regeneration after partial hepatectomy has been studied extensively since the 19th century, establishing the long-standing model that hepatocytes, which account for most of the liver weight, proliferate to recover the original mass of the liver. The basis of this model is the fact that almost all hepatocytes undergo S phase, as shown by the incorporation of radioactive nucleotides during liver regeneration. However, DNA replication does not necessarily indicate the execution of cell division, and a possible change in hepatocyte size is not considered in the model. In addition, as 15–30% of hepatocytes in adult liver are binuclear, the difference in nuclear number may affect the mode of cell division during regeneration. Thus, the traditional model seems to be oversimplified. Recently, we developed new techniques to investigate the process of liver regeneration, and revealed interesting features of hepatocytes. In this review, we first provide a historical overview of how the widely accepted model of liver regeneration was established and then discuss some overlooked observations together with our recent findings. Finally, we describe the revised model and perspectives on liver regeneration research.

【 授权许可】

   
2013 Miyaoka and Miyajima; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Palmes D, Spiegel HU: Animal models of liver regeneration. Biomaterials 2004, 25:1601-1611.
  • [2]Alison MR, Islam S, Lim S: Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly. J Pathol 2009, 217:282-298.
  • [3]Si-Tayeb K, Lemaigre FP, Duncan SA: Organogenesis and development of the liver. Dev Cell 2010, 18:175-189.
  • [4]Zaret KS, Grompe M: Generation and regeneration of cells of the liver and pancreas. Science 2008, 322:1490-1494.
  • [5]Tanaka M, Itoh T, Tanimizu N, Miyajima A: Liver stem/progenitor cells: their characteristics and regulatory mechanisms. J Biochem 2011, 149:231-239.
  • [6]Court FG, Wemyss-Holden SA, Dennison AR, Maddern GJ: The mystery of liver regeneration. Br J Surg 2002, 89:1089-1095.
  • [7]Fausto N: Liver regeneration. J Hepatol 2000, 32:19-31.
  • [8]Michalopoulos GK: Liver regeneration. J Cell Physiol 2007, 213:286-300.
  • [9]Michalopoulos GK, DeFrances M: Liver regeneration. Adv Biochem Eng Biotechnol 2005, 93:101-134.
  • [10]Brockes JP, Kumar A: Comparative aspects of animal regeneration. Annu Rev Cell Dev Biol 2008, 24:525-549.
  • [11]Milne LS: The histology of liver tissue regeneration. J Pathol Bacteriol 1909, 13:127-160.
  • [12]Higgins G, Anderson GM: Experimental pathology of the liver. Restoration of the liver of the white rat following partial surgical removal. Arch Pathol 1931, 12:186-202.
  • [13]Beams HW, King RL: The origin of binucleate and large mono nucleate cells in the liver of the rat. Anat Rec 1942, 83:281-297.
  • [14]Sulkin NM: A study of the nucleus in the normal and hyperplastic liver of the rat. Am J Anat 1943, 73:107-125.
  • [15]St Aubin PM, Bucher NL: A study of binucleate cell counts in resting and regenerating rat liver employing a mechanical method for the separation of liver cells. Anat Rec 1952, 112:797-809.
  • [16]Jordan SW: Electron Microscopy of Hepatic Regeneration. Exp Mol Pathol 1964, 86:183-200.
  • [17]Stenger RJ, Confer DB: Hepatocellular ultrastructure during liver regeneration after subtotal hepatectomy. Exp Mol Pathol 1966, 5:455-474.
  • [18]Aterman K: Electron microscopy of the rat liver cell after partial hepatectomy. J Pathol Bacteriol 1961, 82:367-369.
  • [19]Fisher ER, Fisher B: Ultrastructural Hepatic Changes Following Partial Hepatectomy and Portacaval Shunt in the Rat. Lab Invest 1963, 12:929-942.
  • [20]Grisham JW: A morphologic study of deoxyribonucleic acid synthesis and cell proliferation in regenerating rat liver; autoradiography with thymidine-H3. Cancer Res 1962, 22:842-849.
  • [21]Bucher NL, Swaffield MN: The Rate of Incorporation of Labeled Thymidine into the Deoxyribonucleic Acid of Regenerating Rat Liver in Relation to the Amount of Liver Excised. Cancer Res 1964, 24:1611-1625.
  • [22]Fabrikant JI: The kinetics of cellular proliferation in regenerating liver. J Cell Biol 1968, 36:551-565.
  • [23]Bucher NL, Swaffield MN: Rate of incorporation of [6-14C]orotic acid into uridine 5′-triphosphate and cytidine 5′-triphosphate and nuclear ribonucleic acid in regenerating rat liver. Biochim Biophys Acta 1965, 108:551-567.
  • [24]Bucher NL, Oakman NJ: Thymidine triphosphate content of regenerating rat liver. Biochim Biophys Acta 1969, 186:13-20.
  • [25]Stocker E, Pfeifer U: [On the manner of proliferation of the liver parenchyma after partial hepatectomy. Autoradiography studies using 3H-thymidine]. Naturwissenschaften 1965, 52:663.
  • [26]Fausto N, Campbell JS, Riehle KJ: Liver regeneration. Hepatology 2006, 43:S45-S53.
  • [27]Duncan AW, Dorrell C, Grompe M: Stem cells and liver regeneration. Gastroenterology 2009, 137:466-481.
  • [28]Koller BH, Hagemann LJ, Doetschman T, Hagaman JR, Huang S, Williams PJ, First NL, Maeda N, Smithies O: Germ-line transmission of a planned alteration made in a hypoxanthine phosphoribosyltransferase gene by homologous recombination in embryonic stem cells. Proc Natl Acad Sci USA 1989, 86:8927-8931.
  • [29]Schwartzberg PL, Goff SP, Robertson EJ: Germ-line transmission of a c-abl mutation produced by targeted gene disruption in ES cells. Science 1989, 246:799-803.
  • [30]Thompson S, Clarke AR, Pow AM, Hooper ML, Melton DW: Germ line transmission and expression of a corrected HPRT gene produced by gene targeting in embryonic stem cells. Cell 1989, 56:313-321.
  • [31]Tan X, Behari J, Cieply B, Michalopoulos GK, Monga SP: Conditional deletion of beta-catenin reveals its role in liver growth and regeneration. Gastroenterology 2006, 131:1561-1572.
  • [32]Chen L, Zeng Y, Yang H, Lee TD, French SW, Corrales FJ, Garcia-Trevijano ER, Avila MA, Mato JM, Lu SC: Impaired liver regeneration in mice lacking methionine adenosyltransferase 1A. FASEB J 2004, 18:914-916.
  • [33]Nakamura K, Nonaka H, Saito H, Tanaka M, Miyajima A: Hepatocyte proliferation and tissue remodeling is impaired after liver injury in oncostatin M receptor knockout mice. Hepatology 2004, 39:635-644.
  • [34]Beyer TA, Xu W, Teupser D, Auf Dem Keller U, Bugnon P, Hildt E, Thiery J, Kan YW, Werner S: Impaired liver regeneration in Nrf2 knockout mice: role of ROS-mediated insulin/IGF-1 resistance. EMBO J 2008, 27:212-223.
  • [35]Factor VM, Seo D, Ishikawa T, Kaposi-Novak P, Marquardt JU, Andersen JB, Conner EA, Thorgeirsson SS: Loss of c-Met disrupts gene expression program required for G2/M progression during liver regeneration in mice. PLoS One 2010, 5:e12739.
  • [36]Geschwind II, Alfert M, Schooley C: Liver regeneration and hepatic polyploidy in the hypophysectomized rat. Exp Cell Res 1958, 15:232-235.
  • [37]Gentric G, Celton-Morizur S, Desdouets C: Polyploidy and liver proliferation. Clin Res Hepatol Gastroenterol 2012, 36:29-34.
  • [38]Miyaoka Y, Ebato K, Kato H, Arakawa S, Shimizu S, Miyajima A: Hypertrophy and unconventional cell division of hepatocytes underlie liver regeneration. Curr Biol 2012, 22:1166-1175.
  • [39]Herweijer H, Wolff JA: Gene therapy progress and prospects: hydrodynamic gene delivery. Gene Ther 2007, 14:99-107.
  • [40]Wooddell CI, Reppen T, Wolff JA, Herweijer H: Sustained liver-specific transgene expression from the albumin promoter in mice following hydrodynamic plasmid DNA delivery. J Gene Med 2008, 10:551-563.
  • [41]Mitchell C, Nivison M, Jackson LF, Fox R, Lee DC, Campbell JS, Fausto N: Heparin-binding epidermal growth factor-like growth factor links hepatocyte priming with cell cycle progression during liver regeneration. J Biol Chem 2005, 280:2562-2568.
  • [42]Conlon I, Raff M: Size control in animal development. Cell 1999, 96:235-244.
  • [43]Su AI, Guidotti LG, Pezacki JP, Chisari FV, Schultz PG: Gene expression during the priming phase of liver regeneration after partial hepatectomy in mice. Proc Natl Acad Sci USA 2002, 99:11181-11186.
  • [44]Haga S, Ogawa W, Inoue H, Terui K, Ogino T, Igarashi R, Takeda K, Akira S, Enosawa S, Furukawa H, et al.: Compensatory recovery of liver mass by Akt-mediated hepatocellular hypertrophy in liver-specific STAT3-deficient mice. J Hepatol 2005, 43:799-807.
  • [45]Minamishima YA, Nakayama K: Recovery of liver mass without proliferation of hepatocytes after partial hepatectomy in Skp2-deficient mice. Cancer Res 2002, 62:995-999.
  • [46]Wirth KG, Wutz G, Kudo NR, Desdouets C, Zetterberg A, Taghybeeglu S, Seznec J, Ducos GM, Ricci R, Firnberg N, et al.: Separase: a universal trigger for sister chromatid disjunction but not chromosome cycle progression. J Cell Biol 2006, 172:847-860.
  • [47]Diril MK, Ratnacaram CK, Padmakumar VC, Du T, Wasser M, Coppola V, Tessarollo L, Kaldis P: Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration. Proc Natl Acad Sci USA 2012, 109:3826-3831.
  • [48]Nagy P, Teramoto T, Factor VM, Sanchez A, Schnur J, Paku S, Thorgeirsson SS: Reconstitution of liver mass via cellular hypertrophy in the rat. Hepatology 2001, 33:339-345.
  • [49]Trotter NL: A Fine Structure Study of Lipid in Mouse Liver Regenerating after Partial Hepatectomy. J Cell Biol 1964, 21:233-244.
  • [50]Trotter NL: Electron-opaque, lipid-containing bodies in mouse liver at early intervals after partial hepatectomy and sham operation. J Cell Biol 1965, 25(Suppl):41-52.
  • [51]Shteyer E, Liao Y, Muglia LJ, Hruz PW, Rudnick DA: Disruption of hepatic adipogenesis is associated with impaired liver regeneration in mice. Hepatology 2004, 40:1322-1332.
  • [52]Murray AB, Strecker W, Silz S: Ultrastructural changes in rat hepatocytes after partial hepatectomy, and comparison with biochemical results. J Cell Sci 1981, 50:433-448.
  • [53]Kozma SC, Thomas G: Regulation of cell size in growth, development and human disease: PI3K, PKB and S6K. Bioessays 2002, 24:65-71.
  • [54]Kim S, Li Q, Dang CV, Lee LA: Induction of ribosomal genes and hepatocyte hypertrophy by adenovirus-mediated expression of c-Myc in vivo. Proc Natl Acad Sci USA 2000, 97:11198-11202.
  • [55]Beer S, Zetterberg A, Ihrie RA, McTaggart RA, Yang Q, Bradon N, Arvanitis C, Attardi LD, Feng S, Ruebner B, et al.: Developmental context determines latency of MYC-induced tumorigenesis. PLoS Biol 2004, 2:e332.
  • [56]Baena E, Gandarillas A, Vallespinos M, Zanet J, Bachs O, Redondo C, Fabregat I, Martinez AC, De Alboran IM: c-Myc regulates cell size and ploidy but is not essential for postnatal proliferation in liver. Proc Natl Acad Sci USA 2005, 102:7286-7291.
  • [57]Ruvinsky I, Meyuhas O: Ribosomal protein S6 phosphorylation: from protein synthesis to cell size. Trends Biochem Sci 2006, 31:342-348.
  • [58]Jorgensen P, Tyers M: How cells coordinate growth and division. Curr Biol 2004, 14:R1014-R1027.
  • [59]Gentric G, Desdouets C, Celton-Morizur S: Hepatocytes polyploidization and cell cycle control in liver physiopathology. Int J Hepatol 2012, 2012:282430.
  • [60]Celton-Morizur S, Merlen G, Couton D, Desdouets C: Polyploidy and liver proliferation: central role of insulin signaling. Cell Cycle 2010, 9:460-466.
  • [61]Celton-Morizur S, Merlen G, Couton D, Margall-Ducos G, Desdouets C: The insulin/Akt pathway controls a specific cell division program that leads to generation of binucleated tetraploid liver cells in rodents. J Clin Invest 2009, 119:1880-1887.
  • [62]Satyanarayana A, Wiemann SU, Buer J, Lauber J, Dittmar KEJ, Wustefeld T, Blasco MA, Manns MP, Rudolph KL: Telomere shortening impairs organ regeneration by inhibiting cell cycle re-entry of a subpopulation of cells. EMBO J 2003, 22:4003-4013.
  • [63]Enserink JM, Kolodner RD: An overview of Cdk1-controlled targets and processes. Cell Div 2010, 5:11. BioMed Central Full Text
  • [64]Bloom J, Cross FR: Multiple levels of cyclin specificity in cell-cycle control. Nat Rev Mol Cell Biol 2007, 8:149-160.
  • [65]Norbury C, Blow J, Nurse P: Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates. EMBO J 1991, 10:3321-3329.
  • [66]Lee HO, Davidson JM, Duronio RJ: Endoreplication: polyploidy with purpose. Genes Dev 2009, 23:2461-2477.
  • [67]Chen HZ, Ouseph MM, Li J, Pecot T, Chokshi V, Kent L, Bae S, Byrne M, Duran C, Comstock G, et al.: Canonical and atypical E2Fs regulate the mammalian endocycle. Nat Cell Biol 2012, 14:1192-1202.
  • [68]Pandit SK, Westendorp B, Nantasanti S, Van Liere E, Tooten PC, Cornelissen PW, Toussaint MJ, Lamers WH, de Bruin A: E2F8 is essential for polyploidization in mammalian cells. Nat Cell Biol 2012, 14:1181-1191.
  • [69]Harrison MF: Percentage of binucleate cells in the livers of adult rats. Nature 1953, 171:611.
  • [70]Wheatley DN: Binucleation in mammalian liver. Studies on the control of cytokinesis in vivo. Exp Cell Res 1972, 74:455-465.
  • [71]Gerlyng P, Abyholm A, Grotmol T, Erikstein B, Huitfeldt HS, Stokke T, Seglen PO: Binucleation and polyploidization patterns in developmental and regenerative rat liver growth. Cell Prolif 1993, 26:557-565.
  • [72]Yu JT, Foster RG, Dean DC: Transcriptional repression by RB-E2F and regulation of anchorage-independent survival. Mol Cell Biol 2001, 21:3325-3335.
  • [73]Brennan P, Babbage JW, Burgering BM, Groner B, Reif K, Cantrell DA: Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F. Immunity 1997, 7:679-689.
  • [74]Ruchaud S, Carmena M, Earnshaw WC: Chromosomal passengers: conducting cell division. Nat Rev Mol Cell Biol 2007, 8:798-812.
  • [75]Guidotti JE, Bregerie O, Robert A, Debey P, Brechot C, Desdouets C: Liver cell polyploidization: a pivotal role for binuclear hepatocytes. J Biol Chem 2003, 278:19095-19101.
  • [76]Duncan AW, Taylor MH, Hickey RD, Hanlon Newell AE, Lenzi ML, Olson SB, Finegold MJ, Grompe M: The ploidy conveyor of mature hepatocytes as a source of genetic variation. Nature 2010, 467:707-710.
  • [77]Thornburg K, Jonker S, O'Tierney P, Chattergoon N, Louey S, Faber J, Giraud G: Regulation of the cardiomyocyte population in the developing heart. Prog Biophys Mol Biol 2011, 106:289-299.
  • [78]Liu Z, Yue S, Chen X, Kubin T, Braun T: Regulation of cardiomyocyte polyploidy and multinucleation by CyclinG1. Circ Res 2010, 106:1498-1506.
  • [79]Sedmera D, Thompson RP: Myocyte proliferation in the developing heart. Dev Dyn 2011, 240:1322-1334.
  • [80]Bersell K, Arab S, Haring B, Kuhn B: Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury. Cell 2009, 138:257-270.
  • [81]Duncan AW, Hanlon Newell AE, Smith L, Wilson EM, Olson SB, Thayer MJ, Strom SC, Grompe M: Frequent aneuploidy among normal human hepatocytes. Gastroenterology 2012, 142:25-28.
  • [82]Lu P, Prost S, Caldwell H, Tugwood JD, Betton GR, Harrison DJ: Microarray analysis of gene expression of mouse hepatocytes of different ploidy. Mamm Genome 2007, 18:617-626.
  • [83]Anatskaya OV, Vinogradov AE: Genome multiplication as adaptation to tissue survival: evidence from gene expression in mammalian heart and liver. Genomics 2007, 89:70-80.
  • [84]Martin NC, McCullough CT, Bush PG, Sharp L, Hall AC, Harrison DJ: Functional analysis of mouse hepatocytes differing in DNA content: volume, receptor expression, and effect of IFNgamma. J Cell Physiol 2002, 191:138-144.
  • [85]Sigal SH, Rajvanshi P, Gorla GR, Sokhi RP, Saxena R, Gebhard DR Jr, Reid LM, Gupta S: Partial hepatectomy-induced polyploidy attenuates hepatocyte replication and activates cell aging events. Am J Physiol 1999, 276:G1260-G1272.
  • [86]Fankhauser G: Maintenance of normal structure in heteroploid salamander larvae, through compensation of changes in cell size by adjustment of cell number and cell shape. J Exp Zool 1945, 100:445-455.
  • [87]Henery CC, Bard JB, Kaufman MH: Tetraploidy in mice, embryonic cell number, and the grain of the developmental map. Dev Biol 1992, 152:233-241.
  • [88]Holland AJ, Cleveland DW: Losing balance: the origin and impact of aneuploidy in cancer. EMBO Rep 2012, 13:501-514.
  • [89]Pfau SJ, Amon A: Chromosomal instability and aneuploidy in cancer: from yeast to man. EMBO Rep 2012, 13:515-527.
  • [90]Lazzerini Denchi E, Celli G, de Lange T: Hepatocytes with extensive telomere deprotection and fusion remain viable and regenerate liver mass through endoreduplication. Genes Dev 2006, 20:2648-2653.
  • [91]Raff MC: Size control: the regulation of cell numbers in animal development. Cell 1996, 86:173-175.
  • [92]Savage VM, Allen AP, Brown JH, Gillooly JF, Herman AB, Woodruff WH, West GB: Scaling of number, size, and metabolic rate of cells with body size in mammals. Proc Natl Acad Sci USA 2007, 104:4718-4723.
  • [93]Liu B, Preisig PA: Compensatory renal hypertrophy is mediated by a cell cycle-dependent mechanism. Kidney Int 2002, 62:1650-1658.
  • [94]Harvey PA, Leinwand LA: The cell biology of disease: cellular mechanisms of cardiomyopathy. J Cell Biol 2011, 194:355-365.
  • [95]Watkins H, Ashrafian H, Redwood C: Inherited cardiomyopathies. N Engl J Med 2011, 364:1643-1656.
  • [96]Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford SA, Gayyed MF, Anders RA, Maitra A, Pan D: Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 2007, 130:1120-1133.
  • [97]Song H, Mak KK, Topol L, Yun K, Hu J, Garrett L, Chen Y, Park O, Chang J, Simpson RM, et al.: Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression. Proc Natl Acad Sci USA 2010, 107:1431-1436.
  • [98]Tumaneng K, Russell RC, Guan KL: Organ size control by Hippo and TOR pathways. Curr Biol 2012, 22:R368-R379.
  • [99]Pan D: Hippo signaling in organ size control. Genes Dev 2007, 21:886-897.
  • [100]Tordjmann T: Hippo signalling: liver size regulation and beyond. Clin Res Hepatol Gastroenterol 2011, 35:344-346.
  • [101]Tumaneng K, Schlegelmilch K, Russell RC, Yimlamai D, Basnet H, Mahadevan N, Fitamant J, Bardeesy N, Camargo FD, Guan KL: YAP mediates crosstalk between the Hippo and PI(3)K-TOR pathways by suppressing PTEN via miR-29. Nat Cell Biol 2012, 14:1322-1329.
  • [102]Wang HH, Lautt WW: Evidence of nitric oxide, a flow-dependent factor, being a trigger of liver regeneration in rats. Can J Physiol Pharmacol 1998, 76:1072-1079.
  • [103]Schoen JM, Wang HH, Minuk GY, Lautt WW: Shear stress-induced nitric oxide release triggers the liver regeneration cascade. Nitric Oxide 2001, 5:453-464.
  • [104]Macedo MP, Lautt WW: Shear-induced modulation of vasoconstriction in the hepatic artery and portal vein by nitric oxide. Am J Physiol 1998, 274:G253-G260.
  • [105]Sato Y, Tsukada K, Hatakeyama K: Role of shear stress and immune responses in liver regeneration after a partial hepatectomy. Surg Today 1999, 29:1-9.
  • [106]Niiya T, Murakami M, Aoki T, Murai N, Shimizu Y, Kusano M: Immediate increase of portal pressure, reflecting sinusoidal shear stress, induced liver regeneration after partial hepatectomy. J Hepatobiliary Pancreat Surg 1999, 6:275-280.
  • [107]Huang W, Ma K, Zhang J, Qatanani M, Cuvillier J, Liu J, Dong B, Huang X, Moore DD: Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration. Science 2006, 312:233-236.
  • [108]Meng Z, Liu N, Fu X, Wang X, Wang YD, Chen WD, Zhang L, Forman BM, Huang W: Insufficient bile acid signaling impairs liver repair in CYP27(−/−) mice. J Hepatol 2011, 55:885-895.
  • [109]Holecek M: Nutritional modulation of liver regeneration by carbohydrates, lipids, and amino acids: a review. Nutrition 1999, 15:784-788.
  • [110]Simek J, Chmelar V, Melka J, Pazderka , Charvat Z: Influence of protracted infusion of glucose and insulin on the composition and regeneration activity of liver after partial hepatectomy in rats. Nature 1967, 213:910-911.
  • [111]Simek J, Melka J, Pospisil M, Neradilkova M: Effect of protracted glucose infusion on the development of early biochemical changes and initiation of regeneration in rat liver after partial hepatectomy. Physiol Bohemoslov 1965, 14:366-370.
  • [112]Weymann A, Hartman E, Gazit V, Wang C, Glauber M, Turmelle Y, Rudnick DA: p21 is required for dextrose-mediated inhibition of mouse liver regeneration. Hepatology 2009, 50:207-215.
  • [113]Carr BI, Hayashi I, Branum EL, Moses HL: Inhibition of DNA synthesis in rat hepatocytes by platelet-derived type beta transforming growth factor. Cancer Res 1986, 46:2330-2334.
  • [114]Apte U, Gkretsi V, Bowen WC, Mars WM, Luo JH, Donthamsetty S, Orr A, Monga SP, Wu C, Michalopoulos GK: Enhanced liver regeneration following changes induced by hepatocyte-specific genetic ablation of integrin-linked kinase. Hepatology 2009, 50:844-851.
  • [115]Liu B, Bell AW, Paranjpe S, Bowen WC, Khillan JS, Luo JH, Mars WM, Michalopoulos GK: Suppression of liver regeneration and hepatocyte proliferation in hepatocyte-targeted glypican 3 transgenic mice. Hepatology 2010, 52:1060-1067.
  • [116]Liu B, Paranjpe S, Bowen WC, Bell AW, Luo JH, Yu YP, Mars WM, Michalopoulos GK: Investigation of the role of glypican 3 in liver regeneration and hepatocyte proliferation. Am J Pathol 2009, 175:717-724.
  • [117]Yamamoto Y, Ono T, Dhar DK, Yamanoi A, Tachibana M, Tanaka T, Nagasue N: Role of peroxisome proliferator-activated receptor-gamma (PPARgamma) during liver regeneration in rats. J Gastroenterol Hepatol 2008, 23:930-937.
  • [118]Nygard IE, Mortensen KE, Hedegaard J, Conley LN, Kalstad T, Bendixen C, Revhaug A: The genetic regulation of the terminating phase of liver regeneration. Comp Hepatol 2012, 11:3. BioMed Central Full Text
  • [119]Rychtrmoc D, Hubalkova L, Viskova A, Libra A, Buncek M, Cervinkova Z: Transcriptome temporal and functional analysis of liver regeneration termination. Physiol Res 2012, 61(Suppl 2):S77-S92.
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