pp. Jak STAT PDK Akt The molecular mechanism of liver injury regeneration an analysis by bio-imaging Michitaka Ozaki Faculty of Health Sciences, Hokkaido University Graduate School of Medicine, N-, W-, Kitaku, Sapporo, Hokkaido, Japan
T triiodothyronine AChLPSEGF TLR Toll HGFGHIGF-- Kupffer cell KChepatic stellate cell HSChepatic endothelial cell HEC - IL--
α TNF-α HGF LPS TNF-α NFκB IL- TNF-α HSC HEC HGF HGF c-metpi -K Akt MAPK T Jak STAT PI -K Akt STATs signal transducers and activators of transcription STAT STATIL- Jak STAT Taub STAT IL- STAT STATIL- gp Jak DNA IL- STAT STAT STAT STAT D cyclind Akt GSK- mtor p S K STAT STAT STAT L-S KO
STAT STAT Akt -phosphoinositide-dependent protein kinase PDK PDK STAT PDK PDK STAT PDK Jak STAT PDK PDK PI -K myr-p PDKAkt STAT STAT PDK Jak STAT PDK PDK PDK pif S S K serum and glucocorticoid induced kinase SGK HM hydrophobic motif -kinase PDK PDK p S K SGK Akt PDK
PDK PDK LacZ β myr-p PI -K pfu body Jak STAT PI -K PDK STAT PDK p S K Jak STAT PDK Akt Akt Akt STAT STAT Akt Jak STAT PDK Akt STAT D STATRef- Mn-SOD Bcl- xl FLIP Fas-L Fas STAT Fas-L Jo STAT STAT STAT STAT Bcl- Bcl-xL FLIP FLICE inhibitor protein FLICE - Fas-L Fas NAC N - STAT Mn-SOD Ref- STAT a b c HGF PI -K
STAT PDK Akt STAT Akt Akt PI -K Akt Akt FKHR Bcl- -associated death protein BAD - GSK- β Fas-L Bcl- Akt Rac Akt HGF Rac Akt Akt STAT - - DEVD - GFP reduction-oxidation-sensitive GFP rogfp a MAPK STAT Akt
rogfp- - p SHC Akt SHC src homology domain-containing transforming protein C Ras MAP EGF p SHC p SHC p SHC b db db Wee Myt- Cdc
Taub, R.Nat. Rev. Mol. Cell. Biol.,,. Yokoyama, Y., Nagino, M., & Nimura, Y.J. Hepatobiliary Pancreat. Surg.,,. Murata, H., Yagi, T., Iwagaki, H., Ogino, T., Sadamori, H., Matsukawa, H., Umeda, Y., Haga, S., Takaka, N., & Ozaki, M. J. Gastroenterol. Hepatol.,,. Devi, S.S. & Mehendale, H.M.Eur. J. Pharmacol.,,. Schmucker, D.L.Exp. Gerontol.,,. Fausto, N.Liver Transpl.,,. White, P., Brestelli, J.E., Kaestner, K.H., & Greenbaum, L.E. J. Biol. Chem.,,. Diehl, A.M. & Rai, R.M.FASEB J.,,. Higgins, G.M. & Anderson, R.M.Arch. Pathol.,,. Taub, R.FASEB J.,,. Brenner, D.A.J. Gastroenterol. Hepatol.,, SS. Baier, P.K., Baumgartner, U., Hempel, S., Wolff-Vorbeck, G., von Dobschuetz, E., & Hopt, U.T.Eur. Surg. Res.,,. Kiba, T.Digestion,,. Moro, L., Marra, E., Capuano, F., & Greco, M.Endocrinology,,. Kopplow, K., Waysms, K., Enzmann, H., & Mayer, D. Int. J. Oncol.,,. Tang, T.X., Hashimoto, T., Chao, L.Y., Itoh, K., & Manabe, T. J. Surg. Res.,,. Marti, U., Burwen, S.J., & Jones, A.L.Hepatology,,. Zimmers, T.A., McKillop, I.H., Pierce, R.H., Yoo, J.Y., & Koniaris, L.G.Hepatology,,. Freedman, A.R., Sharma, R.J., Nabel, G.J., Emerson, S.G., & Griffin, G.E.Biochem. J.,,. Pennisi, P.A., Kopchick, J.J., Thorgeirsson, S., LeRoith, D., & Yakar, S.Endocrinology,,. Darnell, J.E, Kerr, I.M., & Stark, G.R.Science,,. Blindenbacher, A., Wang, X., Langer, I., Savino, R., Terracciano,L.,&Heim,M.H.Hepatology,,. Darnell, J.E.Science,,. Cressman, D.E., Diamond, R.H., & Taub, R.Hepatology,,. Cressman, D.E., Greenbaum, L.E., DeAngelis, R.A., Ciliberto, G., Furth, E.E., Poli, V., & Taub, R.Science,,. Haga, S., Ogawa, W., Inoue, H., Terui, K., Ogino, T., Igarashi, R., Takeda, K., Akira, S., Enosawa, S., Furukawa, H., Todo, S., & Ozaki, M.J. Hepatol.,,. Haga, S., Ozaki, M., Inoue, H., Okamoto, Y., Ogawa, W., Takeda, K., Akira, S., & Todo, S.Hepatology,,. Haga, S., Terui, K., Zhang, H.Q., Enosawa, S., Ogawa, W., Inoue, H., Okuyama, T., Takeda, K., Akira, S., Ogino, T., Irani, K., & Ozaki, M.J. Clin. Invest.,,. Jaeschke, H., Gores, G.J., Cederbaum, A.I., Hinson, J.A., Pessayre, D., & Lemasters, J.J.Toxicol. Sci.,,. Wang, H., Xu, D.X., Lu, J.W., Zhao, L., Zhang, C., & Wei, W.Acta Pharmacol. Sin.,,. Terui, K., Enosawa, S., Haga, S., Zhang, H.Q., Kuroda, H., Kouchi, K., Matsunaga, T., Yoshida, H., Engelhardt, J.F., Irani, K., Ohnuma, N., & Ozaki, M.J. Hepatol.,,. Brunet, A., Bonni, A., Zigmond, M.J., Lin, M.Z., Juo, P., Hu, L.S., Anderson, M.J., Arden, K.C., Blenis, J., & Greenberg, M. E.Cell,,. Nair, V.D. & Olanow, C.W. J. Biol. Chem.,,. Ozaki, M., Haga, S., Zhang, H.Q., Irani, K., & Suzuki, S. Cell Death Differ.,,. Kanno, A., Yamanaka, Y., Hirano, H., Umezawa, Y., & Ozawa, T.Angew. Chem. Int. Ed. Engl.,,. Dooley, C.T., Dore, T.M., Hanson, G.T., Jackson, W.C., Remington, S.J., & Tsien, R.Y.J. Biol. Chem.,,. Krupczak-Hollis, K., Wang, X., Dennewitz, M.B., & Costa, R. H.Hepatology,,. Haga, S., Morita, N., Irani, K., Fujiyoshi, M., Ogino, T., Ozawa, T., & Ozaki, M.Lab. Invest.,,.