Nrf2 Enhances Cholangiocyte Expansion in Pten-Deficient Livers

REFERENCES

• Motohashi H, Yamamoto M. 2004. Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol. Med. 10:549–557. http://dx.doi.org/10.1016/j.molmed.2004.09.003.
   PubMed Web of Science ®Google Scholar
• Hirotsu Y, Katsuoka F, Funayama R, Nagashima T, Nishida Y, Nakayama K, Engel JD, Yamamoto M. 2012. Nrf2-MafG heterodimers contribute globally to antioxidant and metabolic networks. Nucleic Acids Res. 40:10228–10239. http://dx.doi.org/10.1093/nar/gks827.
   PubMed Web of Science ®Google Scholar
• Kobayashi A, Kang MI, Watai Y, Tong KI, Shibata T, Uchida K, Yamamoto M. 2006. Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of Keap1. Mol. Cell. Biol. 26:221–229. http://dx.doi.org/10.1128/MCB.26.1.221-229.2006.
   PubMed Web of Science ®Google Scholar
• Mitsuishi Y, Taguchi K, Kawatani Y, Shibata T, Nukiwa T, Aburatani H, Yamamoto M, Motohashi H. 2012. Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer Cell 22:66–79. http://dx.doi.org/10.1016/j.ccr.2012.05.016.
   PubMed Web of Science ®Google Scholar
• Singh A, Happel C, Manna SK, Acquaah-Mensah G, Carrerero J, Kumar S, Nasipuri P, Krausz KW, Wakabayashi N, Dewi R, Boros LG, Gonzalez FJ, Gabrielson E, Wong KK, Girnun G, Biswal S. 2013. Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis. J. Clin. Invest. 123:2921–2934. http://dx.doi.org/10.1172/JCI66353.
   PubMed Web of Science ®Google Scholar
• Taguchi K, Motohashi H, Yamamoto M. 2011. Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells 16:123–140. http://dx.doi.org/10.1111/j.1365-2443.2010.01473.x.
   PubMed Web of Science ®Google Scholar
• Inoue D, Suzuki T, Mitsuishi Y, Miki Y, Suzuki S, Sugawara S, Watanabe M, Sakurada A, Endo C, Uruno A, Sasano H, Nakagawa T, Satoh K, Tanaka N, Kubo H, Motohashi H, Yamamoto M. 2012. Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma. Cancer Sci. 103:760–766. http://dx.doi.org/10.1111/j.1349-7006.2012.02216.x.
   PubMed Web of Science ®Google Scholar
• Mitsuishi Y, Motohashi H, Yamamoto M. 2012. The Keap1-Nrf2 system in cancers: stress response and anabolic metabolism. Front. Oncol. 2:200. http://dx.doi.org/10.3389/fonc.2012.00200.
   PubMedGoogle Scholar
• Wakabayashi N, Itoh K, Wakabayashi J, Motohashi H, Noda S, Takahashi S, Imakado S, Kotsuji T, Otsuka F, Roop DR, Harada T, Engel JD, Yamamoto M. 2003. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat. Genet. 35:238–245. http://dx.doi.org/10.1038/ng1248.
   PubMed Web of Science ®Google Scholar
• Motohashi H, Katsuoka F, Engel JD, Yamamoto M. 2004. Small Maf proteins serve as transcriptional cofactors for keratinocyte differentiation in the Keap1-Nrf2 regulatory pathway. Proc. Natl. Acad. Sci. U. S. A. 101:6379–6384. http://dx.doi.org/10.1073/pnas.0305902101.
   PubMed Web of Science ®Google Scholar
• Taguchi K, Maher JM, Suzuki T, Kawatani Y, Motohashi H, Yamamoto M. 2010. Genetic analysis of cytoprotective functions supported by graded expression of Keap1. Mol. Cell. Biol. 30:3016–3026. http://dx.doi.org/10.1128/MCB.01591-09.
   PubMed Web of Science ®Google Scholar
• Motohashi H, Fujita R, Takayama M, Inoue A, Katsuoka F, Bresnick EH, Yamamoto M. 2011. Molecular determinants for small Maf protein control of platelet production. Mol. Cell. Biol. 31:151–162. http://dx.doi.org/10.1128/MCB.00798-10.
   PubMedGoogle Scholar
• Satoh H, Moriguchi T, Takai J, Ebina M, Yamamoto M. 2013. Nrf2 prevents initiation but accelerates progression through the Kras signaling pathway during lung carcinogenesis. Cancer Res. 73:4158–4168. http://dx.doi.org/10.1158/0008-5472.CAN-12-4499.
   PubMed Web of Science ®Google Scholar
• DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K, Mangal D, Yu KH, Yeo CJ, Calhoun ES, Scrimieri F, Winter JM, Hruban RH, Iacobuzio-Donahue C, Kern SE, Blair IA, Tuveson DA. 2011. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 475:106–109. http://dx.doi.org/10.1038/nature10189.
   PubMed Web of Science ®Google Scholar
• Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, Ruland J, Penninger JM, Siderovski DP, Mak TW. 1998. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95:29–39. http://dx.doi.org/10.1016/S0092-8674(00)81780-8.
   PubMed Web of Science ®Google Scholar
• Zhang S, Yu D. 2010. PI(3)king apart PTEN′s role in cancer. Clin. Cancer Res. 16:4325–4330. http://dx.doi.org/10.1158/1078-0432.CCR-09-2990.
   PubMed Web of Science ®Google Scholar
• Hu TH, Huang CC, Lin PR, Chang HW, Ger LP, Lin YW, Changchien CS, Lee CM, Tai MH. 2003. Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma. Cancer 97:1929–1940. http://dx.doi.org/10.1002/cncr.11266.
   PubMed Web of Science ®Google Scholar
• Horie Y, Suzuki A, Kataoka E, Sasaki T, Hamada K, Sasaki J, Mizuno K, Hasegawa G, Kishimoto H, Iizuka M, Naito M, Enomoto K, Watanabe S, Mak TW, Nakano T. 2004. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J. Clin. Invest. 113:1774–1783. http://dx.doi.org/10.1172/JCI20513.
   PubMed Web of Science ®Google Scholar
• Xu X, Kobayashi S, Qiao W, Li C, Xiao C, Radaeva S, Stiles B, Wang RH, Ohara N, Yoshino T, LeRoith D, Torbenson MS, Gores GJ, Wu H, Gao B, Deng CX. 2006. Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption of Smad4 and Pten in mice. J. Clin. Invest. 116:1843–1852. http://dx.doi.org/10.1172/JCI27282.
   PubMed Web of Science ®Google Scholar
• Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M, Nabeshima Y. 1997. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun. 236:313–322. http://dx.doi.org/10.1006/bbrc.1997.6943.
   PubMed Web of Science ®Google Scholar
• Okawa H, Motohashi H, Kobayashi A, Aburatani H, Kensler TW, Yamamoto M. 2006. Hepatocyte-specific deletion of the keap1 gene activates Nrf2 and confers potent resistance against acute drug toxicity. Biochem. Biophys. Res. Commun. 339:79–88. http://dx.doi.org/10.1016/j.bbrc.2005.10.185.
   PubMed Web of Science ®Google Scholar
• Postic C, Magnuson MA. 2000. DNA excision in liver by an albumin-Cre transgene occurs progressively with age. Genesis 26:149–150. http://dx.doi.org/10.1002/(SICI)1526-968X(200002)26:2<149::AID-GENE16>3.0.CO;2-V.
   PubMedGoogle Scholar
• Soriano P. 1999. Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat. Genet. 21:70–71. http://dx.doi.org/10.1038/5007.
   PubMed Web of Science ®Google Scholar
• Mura C, Le Gac G, Jacolot S, Ferec C. 2004. Transcriptional regulation of the human HFE gene indicates high liver expression and erythropoiesis coregulation. FASEB J. 18:1922–1924. http://dx.doi.org/10.1096/fj.04-2520fje.
   PubMed Web of Science ®Google Scholar
• Maruyama A, Tsukamoto S, Nishikawa K, Yoshida A, Harada N, Motojima K, Ishii T, Nakane A, Yamamoto M, Itoh K. 2008. Nrf2 regulates the alternative first exons of CD36 in macrophages through specific antioxidant response elements. Arch. Biochem. Biophys. 477:139–145. http://dx.doi.org/10.1016/j.abb.2008.06.004.
   PubMed Web of Science ®Google Scholar
• Watai Y, Kobayashi A, Nagase H, Mizukami M, McEvoy J, Singer JD, Itoh K, Yamamoto M. 2007. Subcellular localization and cytoplasmic complex status of endogenous Keap1. Genes Cells 12:1163–1178. http://dx.doi.org/10.1111/j.1365-2443.2007.01118.x.
   PubMed Web of Science ®Google Scholar
• Yamamoto T, Suzuki T, Kobayashi A, Wakabayashi J, Maher J, Motohashi H, Yamamoto M. 2008. Physiological significance of reactive cysteine residues of Keap1 in determining Nrf2 activity. Mol. Cell. Biol. 28:2758–2770. http://dx.doi.org/10.1128/MCB.01704-07.
   PubMed Web of Science ®Google Scholar
• Tanimizu N, Nishikawa M, Saito H, Tsujimura T, Miyajima A. 2003. Isolation of hepatoblasts based on the expression of Dlk/Pref-1. J. Cell Sci. 116:1775–1786. http://dx.doi.org/10.1242/jcs.00388.
   PubMed Web of Science ®Google Scholar
• Tanaka M, Miyajima A. 2012. Identification and isolation of adult liver stem/progenitor cells. Methods Mol. Biol. 826:25–32. http://dx.doi.org/10.1007/978-1-61779-468-1_3.
   PubMedGoogle Scholar
• Onodera K, Takahashi S, Nishimura S, Ohta J, Motohashi H, Yomogida K, Hayashi N, Engel JD, Yamamoto M. 1997. GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis. Proc. Natl. Acad. Sci. U. S. A. 94:4487–4492. http://dx.doi.org/10.1073/pnas.94.9.4487.
   PubMedGoogle Scholar
• Tanimizu N, Miyajima A. 2004. Notch signaling controls hepatoblast differentiation by altering the expression of liver-enriched transcription factors. J. Cell Sci. 117:3165–3174. http://dx.doi.org/10.1242/jcs.01169.
   PubMed Web of Science ®Google Scholar
• Okabe M, Tsukahara Y, Tanaka M, Suzuki K, Saito S, Kamiya Y, Tsujimura T, Nakamura K, Miyajima A. 2009. Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liver. Development 136:1951–1960. http://dx.doi.org/10.1242/dev.031369.
   PubMed Web of Science ®Google Scholar
• Caperna TJ, Blomberg le A, Garrett WM, Talbot NC. 2011. Culture of porcine hepatocytes or bile duct epithelial cells by inductive serum-free media. In Vitro Cell Dev. Biol. Anim. 47:218–233. http://dx.doi.org/10.1007/s11626-010-9382-3.
   PubMedGoogle Scholar
• Zhang H, Liu H, Dickinson DA, Liu RM, Postlethwait EM, Laperche Y, Forman HJ. 2006. gamma-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells. Free Radic. Biol. Med. 40:1281–1292. http://dx.doi.org/10.1016/j.freeradbiomed.2005.11.005.
   PubMed Web of Science ®Google Scholar
• Usami H, Kusano Y, Kumagai T, Osada S, Itoh K, Kobayashi A, Yamamoto M, Uchida K. 2005. Selective induction of the tumor marker glutathione S-transferase P1 by proteasome inhibitors. J. Biol. Chem. 280:25267–25276. http://dx.doi.org/10.1074/jbc.M501014200.
   PubMedGoogle Scholar
• Tee LB, Kirilak Y, Huang WH, Smith PG, Morgan RH, Yeoh GC. 1996. Dual phenotypic expression of hepatocytes and bile ductular markers in developing and preneoplastic rat liver. Carcinogenesis 17:251–259. http://dx.doi.org/10.1093/carcin/17.2.251.
   PubMedGoogle Scholar
• Rada P, Rojo AI, Chowdhry S, McMahon M, Hayes JD, Cuadrado A. 2011. SCF/{beta}-TrCP promotes glycogen synthase kinase 3-dependent degradation of the Nrf2 transcription factor in a Keap1-independent manner. Mol. Cell. Biol. 31:1121–1133. http://dx.doi.org/10.1128/MCB.01204-10.
   PubMed Web of Science ®Google Scholar
• Chowdhry S, Zhang Y, McMahon M, Sutherland C, Cuadrado A, Hayes JD. 2013. Nrf2 is controlled by two distinct beta-TrCP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity. Oncogene 32:3765–3781. http://dx.doi.org/10.1038/onc.2012.388.
   PubMed Web of Science ®Google Scholar
• Onoyama I, Suzuki A, Matsumoto A, Tomita K, Katagiri H, Oike Y, Nakayama K, Nakayama KI. 2011. Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver. J. Clin. Invest. 121:342–354. http://dx.doi.org/10.1172/JCI40725.
   PubMedGoogle Scholar
• Sugimoto H, Okada K, Shoda J, Warabi E, Ishige K, Ueda T, Taguchi K, Yanagawa T, Nakahara A, Hyodo I, Ishii T, Yamamoto M. 2010. Deletion of nuclear factor-E2-related factor-2 leads to rapid onset and progression of nutritional steatohepatitis in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 298:G283–G294. http://dx.doi.org/10.1152/ajpgi.00296.2009.
   PubMed Web of Science ®Google Scholar
• Shibata T, Kokubu A, Gotoh M, Ojima H, Ohta T, Yamamoto M, Hirohashi S. 2008. Genetic alteration of Keap1 confers constitutive Nrf2 activation and resistance to chemotherapy in gallbladder cancer. Gastroenterology 135:1358–1368. http://dx.doi.org/10.1053/j.gastro.2008.06.082.
   PubMed Web of Science ®Google Scholar
• Padmanabhan B, Tong KI, Ohta T, Nakamura Y, Scharlock M, Ohtsuji M, Kang MI, Kobayashi A, Yokoyama S, Yamamoto M. 2006. Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. Mol. Cell 21:689–700. http://dx.doi.org/10.1016/j.molcel.2006.01.013.
   PubMed Web of Science ®Google Scholar
• Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, Sou YS, Ueno I, Sakamoto A, Tong KI, Kim M, Nishito Y, Iemura S, Natsume T, Ueno T, Kominami E, Motohashi H, Tanaka K, Yamamoto M. 2010. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat. Cell Biol. 12:213–223. http://dx.doi.org/10.1038/ncb2021.
   PubMed Web of Science ®Google Scholar
• Ichimura Y, Waguri S, Sou YS, Kageyama S, Hasegawa J, Ishimura R, Saito T, Yang Y, Kouno T, Fukutomi T, Hoshii T, Hirao A, Takagi K, Mizushima T, Motohashi H, Lee MS, Yoshimori T, Tanaka K, Yamamoto M, Komatsu M. 2013. Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Mol. Cell 51:618–631. http://dx.doi.org/10.1016/j.molcel.2013.08.003.
   PubMed Web of Science ®Google Scholar
• Suzuki T, Shibata T, Takaya K, Shiraishi K, Kohno T, Kunitoh H, Tsuta K, Furuta K, Goto K, Hosoda F, Sakamoto H, Motohashi H, Yamamoto M. 2013. Regulatory nexus of synthesis and degradation deciphers cellular Nrf2 expression levels. Mol. Cell. Biol. 33:2402–2412. http://dx.doi.org/10.1128/MCB.00065-13.
   PubMed Web of Science ®Google Scholar
• Cho HY, Jedlicka AE, Reddy SP, Kensler TW, Yamamoto M, Zhang LY, Kleeberger SR. 2002. Role of NRF2 in protection against hyperoxic lung injury in mice. Am. J. Respir. Cell Mol. Biol. 26:175–182. http://dx.doi.org/10.1165/ajrcmb.26.2.4501.
   PubMed Web of Science ®Google Scholar
• Wang C, Cui Y, Li C, Zhang Y, Xu S, Li X, Li H, Zhang X. 2013. Nrf2 deletion causes “benign” simple steatosis to develop into nonalcoholic steatohepatitis in mice fed a high-fat diet. Lipids Health Dis. 12:165. http://dx.doi.org/10.1186/1476-511X-12-165.
   PubMedGoogle Scholar
• Kennedy AR, Pissios P, Otu H, Roberson R, Xue B, Asakura K, Furukawa N, Marino FE, Liu FF, Kahn BB, Libermann TA, Maratos-Flier E. 2007. A high-fat, ketogenic diet induces a unique metabolic state in mice. Am. J. Physiol. Endocrinol. Metab. 292:E1724–E1739. http://dx.doi.org/10.1152/ajpendo.00717.2006.
   PubMed Web of Science ®Google Scholar
• Zhong B, Zhou Q, Toivola DM, Tao GZ, Resurreccion EZ, Omary MB. 2004. Organ-specific stress induces mouse pancreatic keratin overexpression in association with NF-kappaB activation. J. Cell Sci. 117:1709–1719. http://dx.doi.org/10.1242/jcs.01016.
   PubMed Web of Science ®Google Scholar
• Takamura A, Komatsu M, Hara T, Sakamoto A, Kishi C, Waguri S, Eishi Y, Hino O, Tanaka K, Mizushima N. 2011. Autophagy-deficient mice develop multiple liver tumors. Genes Dev. 25:795–800. http://dx.doi.org/10.1101/gad.2016211.
   PubMed Web of Science ®Google Scholar
• Cole SE, Wiltshire T, Rue EE, Morrow D, Hieter P, Brahe C, Fisher EM, Katsanis N, Reeves RH. 1999. High-resolution comparative physical mapping of mouse chromosome 10 in the region of homology with human chromosome 21. Mamm. Genome 10:229–234. http://dx.doi.org/10.1007/s003359900978.
   PubMedGoogle Scholar
• Murakami S, Shimizu R, Romeo P-H, Yamamoto M, Motohashi H. Keap1-Nrf2 system regulates cell fate determination of hematopoietic stem cells. Genes Cells, in press.
   Google Scholar