Ekihiro Seki

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc CCR1 and CCR5 promote hepatic fibrosis in mice
    Ekihiro Seki
    Department of Medicine, Columbia University, New York, New York 10032, USA
    J Clin Invest 119:1858-70. 2009
  2. pmc A liver full of JNK: signaling in regulation of cell function and disease pathogenesis, and clinical approaches
    Ekihiro Seki
    Department of Medicine, University of California, La Jolla, CA, USA
    Gastroenterology 143:307-20. 2012
  3. pmc Role of innate immunity and the microbiota in liver fibrosis: crosstalk between the liver and gut
    Ekihiro Seki
    Division of Gastroenterology, Department of Medicine, University of California, San Diego, School of Medicine, 9500 Gilman Drive, MC no 0702, Leichtag Biomedical Research Building, Room no 118B, La Jolla, CA 92093 0702, USA
    J Physiol 590:447-58. 2012
  4. pmc CCR2 promotes hepatic fibrosis in mice
    Ekihiro Seki
    Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093 0702, USA
    Hepatology 50:185-97. 2009
  5. doi request reprint Toll-like receptors and adaptor molecules in liver disease: update
    Ekihiro Seki
    Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA
    Hepatology 48:322-35. 2008
  6. pmc Role and cellular source of nicotinamide adenine dinucleotide phosphate oxidase in hepatic fibrosis
    Samuele De Minicis
    Department of Medicine, University of California San Diego, School of Medicine, San Diego, CA 92093 0602, USA
    Hepatology 52:1420-30. 2010
  7. pmc Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis
    Sayaka Inokuchi
    Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093 0702, USA
    Proc Natl Acad Sci U S A 107:844-9. 2010
  8. ncbi request reprint Alpha-1 antitrypsin Z protein (PiZ) increases hepatic fibrosis in a murine model of cholestasis
    Ali Mencin
    Department of Pediatrics, Morgan Stanley Children s Hospital of New York, Columbia University, College of Physicians and Surgeons, New York, NY, USA
    Hepatology 46:1443-52. 2007
  9. pmc The nicotinamide adenine dinucleotide phosphate oxidase (NOX) homologues NOX1 and NOX2/gp91(phox) mediate hepatic fibrosis in mice
    Yong Han Paik
    Department of Medicine, University of California San Diego, La Jolla, CA, USA
    Hepatology 53:1730-41. 2011
  10. pmc c-Jun N-terminal kinase-1 from hematopoietic cells mediates progression from hepatic steatosis to steatohepatitis and fibrosis in mice
    Yuzo Kodama
    Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA
    Gastroenterology 137:1467-1477.e5. 2009

Collaborators

Detail Information

Publications39

  1. pmc CCR1 and CCR5 promote hepatic fibrosis in mice
    Ekihiro Seki
    Department of Medicine, Columbia University, New York, New York 10032, USA
    J Clin Invest 119:1858-70. 2009
    ..Our data therefore support a role for the CC chemokine system in hepatic fibrogenesis and suggest distinct roles for CCR1 and CCR5 in Kupffer cells and HSCs...
  2. pmc A liver full of JNK: signaling in regulation of cell function and disease pathogenesis, and clinical approaches
    Ekihiro Seki
    Department of Medicine, University of California, La Jolla, CA, USA
    Gastroenterology 143:307-20. 2012
    ..We review the functions and pathways of JNK in liver physiology and pathology and discuss findings from preclinical studies with JNK inhibitors...
  3. pmc Role of innate immunity and the microbiota in liver fibrosis: crosstalk between the liver and gut
    Ekihiro Seki
    Division of Gastroenterology, Department of Medicine, University of California, San Diego, School of Medicine, 9500 Gilman Drive, MC no 0702, Leichtag Biomedical Research Building, Room no 118B, La Jolla, CA 92093 0702, USA
    J Physiol 590:447-58. 2012
    ..This review summarizes recent studies investigating the role of TLRs, intestinal microbiota and bacterial translocation in liver fibrosis, alcoholic liver disease and non-alcoholic steatohepatitis...
  4. pmc CCR2 promotes hepatic fibrosis in mice
    Ekihiro Seki
    Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093 0702, USA
    Hepatology 50:185-97. 2009
    ..Conclusion: Our results indicate that CCR2 promotes HSC chemotaxis and the development of hepatic fibrosis...
  5. doi request reprint Toll-like receptors and adaptor molecules in liver disease: update
    Ekihiro Seki
    Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA
    Hepatology 48:322-35. 2008
    ..We further discuss recent advances regarding cytosolic pattern recognition receptors, RNA helicases that represents a new concept in chronic hepatitis C virus infection...
  6. pmc Role and cellular source of nicotinamide adenine dinucleotide phosphate oxidase in hepatic fibrosis
    Samuele De Minicis
    Department of Medicine, University of California San Diego, School of Medicine, San Diego, CA 92093 0602, USA
    Hepatology 52:1420-30. 2010
    ..Cultured WT and p47phox KO hepatocytes treated with free fatty acids had a similar increase in lipid accumulation. Free fatty acids promoted a 1.5-fold increase in ROS production both in p47phox KO and in WT hepatocytes...
  7. pmc Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis
    Sayaka Inokuchi
    Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093 0702, USA
    Proc Natl Acad Sci U S A 107:844-9. 2010
    ....
  8. ncbi request reprint Alpha-1 antitrypsin Z protein (PiZ) increases hepatic fibrosis in a murine model of cholestasis
    Ali Mencin
    Department of Pediatrics, Morgan Stanley Children s Hospital of New York, Columbia University, College of Physicians and Surgeons, New York, NY, USA
    Hepatology 46:1443-52. 2007
    ..02, P = 0.02). Increased apoptosis was also noted in PiZ BDL mice by terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) and cleaved caspase-3 histological staining...
  9. pmc The nicotinamide adenine dinucleotide phosphate oxidase (NOX) homologues NOX1 and NOX2/gp91(phox) mediate hepatic fibrosis in mice
    Yong Han Paik
    Department of Medicine, University of California San Diego, La Jolla, CA, USA
    Hepatology 53:1730-41. 2011
    ..Both NOX1- and NOX2-deficient HSCs had decreased ROS generation and failed to up-regulate collagen α1(I) and transforming growth factor β in response to angiotensin II...
  10. pmc c-Jun N-terminal kinase-1 from hematopoietic cells mediates progression from hepatic steatosis to steatohepatitis and fibrosis in mice
    Yuzo Kodama
    Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA
    Gastroenterology 137:1467-1477.e5. 2009
    ..However, the mechanism underlying the contribution of JNK to the progression from simple steatosis to steatohepatitis and liver fibrosis is unresolved...
  11. pmc Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2
    Kouichi Miura
    Department of Medicine, School of Medicine, University of California San Diego, La Jolla, USA
    Am J Physiol Gastrointest Liver Physiol 302:G1310-21. 2012
    ..We concluded that CCR2 and Kupffer cells contribute to the progression of NASH by recruiting bone marrow-derived monocytes...
  12. ncbi request reprint Gene expression profiles during hepatic stellate cell activation in culture and in vivo
    Samuele De Minicis
    Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA
    Gastroenterology 132:1937-46. 2007
    ..In this study, we determine gene expression changes in 3 different models of HSC activation and investigate whether HSC culture activation reproduces gene expression changes of HSC in vivo activation...
  13. ncbi request reprint TLR4 enhances TGF-beta signaling and hepatic fibrosis
    Ekihiro Seki
    Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA
    Nat Med 13:1324-32. 2007
    ..Accordingly, Myd88-deficient mice have decreased hepatic fibrosis. Thus, modulation of TGF-beta signaling by a TLR4-MyD88-NF-kappaB axis provides a novel link between proinflammatory and profibrogenic signals...
  14. doi request reprint Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1beta in mice
    Kouichi Miura
    Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, California 92093, USA
    Gastroenterology 139:323-34.e7. 2010
    ..We investigated the role of TLR9 signaling and the inflammatory cytokine interleukin-1beta (IL-1beta) in steatohepatitis, fibrosis, and insulin resistance...
  15. doi request reprint Reduced nicotinamide adenine dinucleotide phosphate oxidase mediates fibrotic and inflammatory effects of leptin on hepatic stellate cells
    Samuele De Minicis
    University of California at San Diego School of Medicine, La Jolla, CA, USA
    Hepatology 48:2016-26. 2008
    ....
  16. ncbi request reprint Systemic mediators induce fibrogenic effects in normal liver after partial bile duct ligation
    Yosuke Osawa
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Liver Int 26:1138-47. 2006
    ..However, it remains unclear if these factors act locally at the site of injury or also affect HSCs distant to the site of injury...
  17. doi request reprint Hepatic stellate cells secrete angiopoietin 1 that induces angiogenesis in liver fibrosis
    Kojiro Taura
    Department of Medicine, School of Medicine, University of California, San Diego, California, USA
    Gastroenterology 135:1729-38. 2008
    ..It functions as an agonist for the receptor tyrosine kinase with immunoglobulin G-like and endothelial growth factor-like domains 2 (Tie2) and counteracts apoptosis, promotes vascular sprouting or branching, and stabilizes vessels...
  18. pmc Transforming growth factor-β signaling in hepatocytes promotes hepatic fibrosis and carcinogenesis in mice with hepatocyte-specific deletion of TAK1
    Ling Yang
    Division of Gastroenterology, Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA
    Gastroenterology 144:1042-1054.e4. 2013
    ..TGF-β activates TAK1 and Smad signaling, which regulate cell death, proliferation, and carcinogenesis. However, it is not clear whether TGF-β signaling in hepatocytes, via TGF-β receptor-2 (Tgfbr2), promotes HCC and liver fibrosis...
  19. pmc Toll-like receptor 2 and palmitic acid cooperatively contribute to the development of nonalcoholic steatohepatitis through inflammasome activation in mice
    Kouichi Miura
    Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, CA, USA
    Hepatology 57:577-89. 2013
    ..In vivo, WT mice on the CDAA diet showed increased caspase-1 activation in the liver and elevated serum levels of IL-1α and IL-1β levels, which were suppressed in TLR2(-/-) mice...
  20. pmc CX3CL1-CX3CR1 interaction prevents carbon tetrachloride-induced liver inflammation and fibrosis in mice
    Tomonori Aoyama
    Division of Gastroenterology, Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093 0702, USA
    Hepatology 52:1390-400. 2010
    ..Finally, CX3CL1 treatment induced the expression of IL-10 and arginase-1 in WT cultured Kupffer cells through CX3CR1, which in turn suppressed HSC activation...
  21. doi request reprint Angiotensin-converting-enzyme 2 inhibits liver fibrosis in mice
    Christoph H Osterreicher
    University of California San Diego, School of Medicine, San Diego, CA 92093 0602, USA
    Hepatology 50:929-38. 2009
    ..Whereas loss of ACE2 activity worsens liver fibrosis in chronic liver injury models, administration of recombinant ACE2 shows therapeutic potential...
  22. pmc Toll-like receptor 4 mediates alcohol-induced steatohepatitis through bone marrow-derived and endogenous liver cells in mice
    Sayaka Inokuchi
    Division of Gastroenterology, Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093 0702, USA
    Alcohol Clin Exp Res 35:1509-18. 2011
    ....
  23. pmc Non-alcoholic steatohepatitis-induced fibrosis: Toll-like receptors, reactive oxygen species and Jun N-terminal kinase
    David A Brenner
    Department of Medicine, UC San Diego Health Sciences, La Jolla, California, USA
    Hepatol Res 41:683-6. 2011
    ..The three pathways are related and synergistic through intracellular cross-talk. Disruption of any of these pathways may inhibit NASH-induced fibrosis and are potential targets for therapeutic intervention...
  24. ncbi request reprint Toll-like receptor signaling in the liver
    Robert F Schwabe
    Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
    Gastroenterology 130:1886-900. 2006
  25. doi request reprint Investigating the role of the extracellular environment in modulating hepatic stellate cell biology with arrayed combinatorial microenvironments
    David A Brafman
    Department of Bioengineering, University of California, San Diego, USA
    Integr Biol (Camb) 1:513-24. 2009
    ..Our results indicate that array-based screens may provide an efficient means for identifying candidate signaling pathways to be targeted for anti-fibrotic therapies...
  26. ncbi request reprint Fatty acid amide hydrolase determines anandamide-induced cell death in the liver
    Soren V Siegmund
    Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA
    J Biol Chem 281:10431-8. 2006
    ..In conclusion, FAAH and GSH are determinants of AEA-mediated cell death in the liver...
  27. ncbi request reprint Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasis
    Hiroshi Uchinami
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Hepatology 44:420-9. 2006
    ....
  28. doi request reprint Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling
    Guobin He
    Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, University of California San Diego, School of Medicine, 9500 Gilman Drive, San Diego, CA 92093, USA
    Cell 155:384-96. 2013
    ..This may be a general mechanism that drives other IL-6-producing malignancies. ..
  29. pmc Toll-like receptors in alcoholic liver disease, non-alcoholic steatohepatitis and carcinogenesis
    Yoon Seok Roh
    Division of Gastroenterology, Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, California 92093 0702, USA
    J Gastroenterol Hepatol 28:38-42. 2013
    ..In this review, we will discuss the role of TLR2, 4, and 9 in Kupffer cells and hepatic stellate cells in the development of ASH, NASH, and hepatocarcinogenesis. ..
  30. pmc p38α inhibits liver fibrogenesis and consequent hepatocarcinogenesis by curtailing accumulation of reactive oxygen species
    Toshiharu Sakurai
    Department of Gastroenterology and Hepatology, Faculty of Medicine, Kinki University, Ohnohigashi, Osaka Sayama, Osaka, Japan
    Cancer Res 73:215-24. 2013
    ..Augmented oxidative stress of liver parenchymal cells may explain the close relationship between liver fibrosis and hepatocarcinogenesis...
  31. ncbi request reprint CYLD and HCC: when being too sensitive to your dirty neighbors results in self-destruction
    Joan Font-Burgada
    Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Cancer Cell 21:711-2. 2012
    ..In this issue of Cancer Cell, Nikolaou et al. show that the deubiquitinating enzyme CYLD is critical for controlling the balance between hepatocyte loss, regeneration, and malignant progression...
  32. pmc Toll-like receptors in liver fibrosis: cellular crosstalk and mechanisms
    Ling Yang
    Division of Gastroenterology, Department of Medicine, University of California San Diego, School of Medicine La Jolla, CA, USA
    Front Physiol 3:138. 2012
    ....
  33. ncbi request reprint Nuclear factor kappa B decoy oligodeoxynucleotides prevent endotoxin-induced fatal liver failure in a murine model
    Ichiro Ogushi
    First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
    Hepatology 38:335-44. 2003
    ..In conclusion, NF-kappa B/decoy/ODN transfer in vivo effectively suppressed endotoxin-induced fatal liver injury in mice...
  34. ncbi request reprint Repeated hepatocyte injury promotes hepatic tumorigenesis in hepatitis C virus transgenic mice
    Takanobu Kato
    Department of Microbiology, Tokyo Metropolitan Institute for Neuroscience, Fucyu, Tokyo 183 8526, Japan
    Cancer Sci 94:679-85. 2003
    ..Furthermore, this experimental mouse model provides a valuable method with which to investigate hepatocarcinogenesis...
  35. ncbi request reprint Contribution of CD1d-unrestricted hepatic DX5+ NKT cells to liver injury in Plasmodium berghei-parasitized erythrocyte-injected mice
    Keishi Adachi
    Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Japan
    Int Immunol 16:787-98. 2004
    ..berghei-induced liver injury. Our studies may have general implications for tissue injuries that are caused by 'bystander killing' or other poorly defined cell-mediated killing mechanisms...
  36. ncbi request reprint ASC is essential for LPS-induced activation of procaspase-1 independently of TLR-associated signal adaptor molecules
    Masatatsu Yamamoto
    Department of Molecular Oncology Division of Molecular and Cellular Biology Institute on Ageing and Adaptation, Shinshu University Graduate School of Medicine, 3 1 1 Asahi, Matsumoto 390 8621, Japan
    Genes Cells 9:1055-67. 2004
    ..These results demonstrate critical roles for ASC in the release of IL-1beta/IL-18 via activation of caspase-1 and provide new insights into the inflammatory responses for host defence and diseases...
  37. ncbi request reprint Contribution of Toll-like receptor/myeloid differentiation factor 88 signaling to murine liver regeneration
    Ekihiro Seki
    First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
    Hepatology 41:443-50. 2005
    ..In conclusion, the TLR/MyD88 pathway is essential for incidental liver restoration, particularly its early phase...
  38. ncbi request reprint Demonstration of cooperative contribution of MET- and EGFR-mediated STAT3 phosphorylation to liver regeneration by exogenous suppressor of cytokine signalings
    Ekihiro Seki
    Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
    J Hepatol 48:237-45. 2008
    ..Here, we investigated this hypothesis by introducing suppressor of cytokine signaling (SOCS)-1 and SOCS3, potent negative regulators of STAT3 signaling, selectively in hepatocytes...
  39. ncbi request reprint Critical roles of myeloid differentiation factor 88-dependent proinflammatory cytokine release in early phase clearance of Listeria monocytogenes in mice
    Ekihiro Seki
    First Department of Surgery and Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Japan
    J Immunol 169:3863-8. 2002
    ..These results indicated a critical role for TLRs/MyD88-dependent IL-12/TNF-alpha production and for IL-12- and IL-18-mediated IFN-gamma production in early phase clearance of LM...

Research Grants1

  1. Synergistic actions by multiple Toll-like receptors in alcoholic liver disease
    Ekihiro Seki; Fiscal Year: 2010
    ..The results from this study will provide the potential targeting for the therapy of alcohol-induced organ pathogenesis including steatohepatitis and brain injury. ..