Liver-specific ablation of integrin-linked kinase in mice results in enhanced and prolonged cell proliferation and hepatomegaly after phenobarbital administration

Toxicological Sciences

Volumn 113, Issue 2, 2009, Pages 358-366

  Donthamsetty, Shashikiran ^a   Bowen, William ^a   Mars, Wendy ^a   Bhave, Vishakha ^a   Luo, Jian Hua ^a   Wu, Cary ^a   Hurd, Jennifer ^a   Orr, Ann ^a   Bell, Aaron ^a   Michalopoulos, George ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

Constitutive androstane receptor; Extracellular matrix; Integrin linked kinase; Integrins; Liver; Phenobarbital

Indexed keywords

5 AMINOLEVULINATE SYNTHASE; ACETYL COENZYME A ACYLTRANSFERASE; ACYL COENZYME A DESATURASE; ALPHA FETOPROTEIN; AQUAPORIN 4; CASPASE 9; CX3C CHEMOKINE; CYCLINE; CYTOCHROME P450 2B6; DRINKING WATER; GAMMA GLUTAMYL HYDROLASE; GLUTAMATE TRANSPORTER; GROWTH FACTOR RECEPTOR BOUND PROTEIN 2; GUANOSINE DIPHOSPHATE MANNOSE; HEPCIDIN; INTEGRIN; INTEGRIN LINKED KINASE; KHELLIN; LEUKEMIA INHIBITORY FACTOR RECEPTOR; LIPOPROTEIN LIPASE; METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE; PHENOBARBITAL; PROCOLLAGEN LYSINE 2 OXOGLUTARATE 5 DIOXYGENASE; SCATTER FACTOR; SPHINGOMYELIN PHOSPHODIESTERASE; SULFOTRANSFERASE; THIOL ESTER HYDROLASE; TRANSFORMING GROWTH FACTOR BETA2; URIDINE PHOSPHORYLASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; CELL PROLIFERATION; CONTROLLED STUDY; DOWN REGULATION; EXTRACELLULAR MATRIX; HEPATOMEGALY; LIVER CELL; LIVER PARENCHYMA; LIVER REGENERATION; LIVER WEIGHT; MOUSE; NONHUMAN; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; TIME; TISSUE SPECIFICITY; UPREGULATION; WILD TYPE;

ANIMALS; CELL PROLIFERATION; HEPATOCYTES; HEPATOMEGALY; LIVER; MICE; MICE, KNOCKOUT; PHENOBARBITAL; PROTEIN-SERINE-THREONINE KINASES;

ANIMALIA; MUS;

EID: 75249102027     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfp281     Document Type: Article

References (25)

1. Apte, U., Gkretsi, V., Bowen, W.C., Mars, W.M., Luo, J.H., Donthamsetty, S., Orr, A., Monga, S.P., Wu, C., and Michalopoulos, G.K. (2009). Enhanced liver regeneration following changes induced by hepatocyte-specific genetic ablation of integrin-linked kinase. Hepatology 50, 844-851.
2. Bell, A.W., and Michalopoulos, G.K. (2006). Phenobarbital regulates nuclear expression of HNF-4alpha in mouse and rat hepatocytes independent of CAR and PXR. Hepatology 44, 186-194.
3. Block, G.D., Locker, J., Bowen, W.C., Petersen, B.E., Katyal, S., Strom, S.C., Riley, T., Howard, T.A., and Michalopoulos, G.K. (1996). Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF/SF, EGF and TGF alpha in a chemically defined (HGM) medium. J. Cell Biol. 132, 1133-1149.
4. Burger, P.C., and Herdson, P.B. (1966). Phenobarbital-induced fine structural changes in rat liver. Am. J. Pathol. 48, 793-809.
5. Carthew, P., Edwards, R.E., and Nolan, B.M. (1998). The quantitative distinction of hyperplasia from hypertrophy in hepatomegaly induced in the rat liver by phenobarbital. Toxicol. Sci. 44, 46-51.
6. Columbano, A., and Shinozuka, H. (1996). Liver regeneration versus direct hyperplasia. FASEB J. 10, 1118-1128.
7. Coni, P., Pichiri-Coni, G., Curto, M., Simbula, G., Giacomini, L., Sarma, D.S., Ledda-Columbano, G.M., and Columbano, A. (1993). Different effects of regenerative and direct mitogenic stimuli on the growth of initiated cells in the resistant hepatocyte model. Jpn. J. Cancer Res. 84, 501-507.
8. Gkretsi, V., Apte, U., Mars, W.M., Bowen, W.C., Luo, J.H., Yang, Y., Yu, Y.P., Orr, A., St-Arnaud, R., Dedhar, S., et al. (2008). Liver-specific ablation of integrin-linked kinase in mice results in abnormal histology, enhanced cell proliferation, and hepatomegaly. Hepatology 48, 1932-1941.
9. Hehlgans, S., Haase, M., and Cordes, N. (2007). Signalling via integrins: implications for cell survival and anticancer strategies. Biochim. Biophys. Acta 1775, 163-180.
10. Kim, T.H., Mars, W.M., Stolz, D.B., Petersen, B.E., and Michalopoulos, G.K. (1997). Extracellular matrix remodeling at the early stages of liver regeneration in the rat. Hepatology 26, 896-904.
11. Lazarevich, N.L., Cheremnova, O.A., Varga, E.V., Ovchinnikov, D.A., Kudrjavtseva, E.I., Morozova, O.V., Fleishman, D.I., Engelhardt, N.V., and Duncan, S.A. (2004). Progression of HCC in mice is associated with a downregulation in the expression of hepatocyte nuclear factors. Hepatology 39, 1038-1047.
12. Ledda-Columbano, G.M., Pibiri, M., Concas, D., Cossu, C., Tripodi, M., and Columbano, A. (2002). Loss of cyclin D1 does not inhibit the proliferative response of mouse liver to mitogenic stimuli. Hepatology 36, 1098-1105.
13. McDonald, P.C., Fielding, A.B., and Dedhar, S. (2008). Integrin-linked kinase-essential roles in physiology and cancer biology. J. Cell Sci. 121, 3121-3132.
14. Michalopoulos, G.K. (2007). Liver regeneration. J. Cell. Physiol. 213, 286-300.
15. Michalopoulos, G.K., and DeFrances, M. (2005). Liver regeneration. Adv. Biochem. Eng. Biotechnol. 93, 101-134.
16. Ross, P.K., Woods, C.G., Bradford, B.U., Kosyk, O., Gatti, D.M., Cunningham, M.L., and Rusyn, I. (2009). Time-course comparison of xenobiotic activators of CAR and PPARalpha in mouse liver. Toxicol. Appl. Pharmacol. 235, 199-207.
17. Rudolph, K.L., Trautwein, C., Kubicka, S., Rakemann, T., Bahr, M.J., Sedlaczek, N., Schuppan, D., and Manns, M.P. (1999). Differential regulation of extracellular matrix synthesis during liver regeneration after partial hepatectomy in rats. Hepatology 30, 1159-1166.
18. Runge, D., Runge, D.M., Daskalakis, N., Lubecki, K.A., Bowen, W.C., and Michalopoulos, G.K. (1999). Matrix-mediated changes in the expression of HNF-4alpha isoforms and in DNA-binding activity of ARP-1 in primary cultures of rat hepatocytes. Biochem. Biophys. Res. Commun. 259, 651-655.
19. Saucedo, L.J., and Edgar, B.A. (2007). Filling out the Hippo pathway. Nat. Rev. Mol. Cell Biol. 8, 613-621.
20. Terpstra, L., Prud'homme, J., Arabian, A., Takeda, S., Karsenty, G., Dedhar, S., and St-Arnaud, R. (2003). Reduced chondrocyte proliferation and chondrodysplasia in mice lacking the integrin-linked kinase in chondrocytes. J. Cell Biol. 162, 139-148.
21. Tsai, W.H., Zarnegar, R., and Michalopoulos, G.K. (1991). Long-term treatment with hepatic tumor promoters inhibits mitogenic responses of hepatocytes to acidic fibroblast growth factor and hepatocyte growth factor. Cancer Lett. 59, 103-108.
22. van Nimwegen, M.J., and van de Water, B. (2007). Focal adhesion kinase: a potential target in cancer therapy. Biochem. Pharmacol. 73, 597-609.
23. Wei, P., Zhang, J., Egan-Hafley, M., Liang, S., and Moore, D.D. (2000). The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism. Nature 407, 920-923.
24. Zhao, B., Lei, Q.Y., and Guan, K.L. (2008). The Hippo-YAP pathway: new connections between regulation of organ size and cancer. Curr. Opin. Cell Biol. 20, 638-646.
25. Zhao, J.D., Jiang, G.L., Hu, W.G., Xu, Z.Y., and Wang, C.F. (2009). Hepatocyte regeneration after partial liver irradiation in rats. Exp. Toxicol. Pathol. 61, 511-518.