David A Brenner

Summary

Affiliation: Columbia University
Country: USA

Publications

  1. ncbi request reprint p18(INK4c) collaborates with other CDK-inhibitory proteins in the regenerating liver
    Tom Luedde
    Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany
    Hepatology 37:833-41. 2003
  2. pmc Fibrocyte-like cells recruited to the spleen support innate and adaptive immune responses to acute injury or infection
    Tatiana Kisseleva
    Department of Medicine, University of California, San Diego, 9500 Gilman Drive 0702, La Jolla, CA 92093, USA
    J Mol Med (Berl) 89:997-1013. 2011
  3. ncbi request reprint Gastrointestinal basic science 2002-2003: the year in review
    David A Brenner
    College of Physicians and Surgeons, Columbia University, 622 West 168th Street, PH 8E 105J, New York, New York 10032, USA
    Clin Gastroenterol Hepatol 2:9-13. 2004
  4. pmc NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis
    Ramon Bataller
    Department of Medicine, Columbia University College of Physicians and Surgeons, 622 West 168th Street, New York, New York 10032, USA
    J Clin Invest 112:1383-94. 2003
  5. 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
  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. ncbi request reprint The role of p70S6K in hepatic stellate cell collagen gene expression and cell proliferation
    Erwin Gabele
    Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7032, USA
    J Biol Chem 280:13374-82. 2005
  8. ncbi request reprint The forkhead transcription factor FoxO1 regulates proliferation and transdifferentiation of hepatic stellate cells
    Masayuki Adachi
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA
    Gastroenterology 132:1434-46. 2007
  9. 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
  10. pmc Migration of fibrocytes in fibrogenic liver injury
    David Scholten
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Am J Pathol 179:189-98. 2011

Detail Information

Publications108 found, 100 shown here

  1. ncbi request reprint p18(INK4c) collaborates with other CDK-inhibitory proteins in the regenerating liver
    Tom Luedde
    Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany
    Hepatology 37:833-41. 2003
    ..Additionally we provide evidence that timing and strength of DNA synthesis in hepatocytes after PH is regulated tightly through the collaboration of different cell cycle inhibitors...
  2. pmc Fibrocyte-like cells recruited to the spleen support innate and adaptive immune responses to acute injury or infection
    Tatiana Kisseleva
    Department of Medicine, University of California, San Diego, 9500 Gilman Drive 0702, La Jolla, CA 92093, USA
    J Mol Med (Berl) 89:997-1013. 2011
    ..Thus, splenic CD45(+)Col(+) cells are a population of rapidly mobilized BM-derived fibrocyte-like cells that respond to inflammation or infection to participate in innate and adaptive immune responses...
  3. ncbi request reprint Gastrointestinal basic science 2002-2003: the year in review
    David A Brenner
    College of Physicians and Surgeons, Columbia University, 622 West 168th Street, PH 8E 105J, New York, New York 10032, USA
    Clin Gastroenterol Hepatol 2:9-13. 2004
    ..New technological advances are being applied to difficult areas of gastrointestinal research. Well-defined patient populations are critical to extend the knowledge derived from the human genome to gastrointestinal diseases...
  4. pmc NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis
    Ramon Bataller
    Department of Medicine, Columbia University College of Physicians and Surgeons, 622 West 168th Street, New York, New York 10032, USA
    J Clin Invest 112:1383-94. 2003
    ..Moreover, expression of smooth muscle alpha-actin and expression of TGF-beta1 were reduced in p47phox-/- mice. Thus, NADPH oxidase mediates the actions of Ang II on HSCs and plays a critical role in liver fibrogenesis...
  5. 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...
  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. ncbi request reprint The role of p70S6K in hepatic stellate cell collagen gene expression and cell proliferation
    Erwin Gabele
    Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7032, USA
    J Biol Chem 280:13374-82. 2005
    ..Together, p70S6K plays a crucial role in HSC proliferation, collagen expression, and cell cycle control, thus representing a potential therapeutic target for liver fibrosis...
  8. ncbi request reprint The forkhead transcription factor FoxO1 regulates proliferation and transdifferentiation of hepatic stellate cells
    Masayuki Adachi
    Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA
    Gastroenterology 132:1434-46. 2007
    ..Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis. A fibrotic stimulus causes HSCs to transdifferentiate from a quiescent phenotype to a collagen-producing myofibroblast-like phenotype and to proliferate...
  9. 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...
  10. pmc Migration of fibrocytes in fibrogenic liver injury
    David Scholten
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Am J Pathol 179:189-98. 2011
    ..In conclusion, in response to liver injury, fibrocytes migrate from BM to the liver. Their migration is regulated by CCR2 and CCR1 but is compromised with age...
  11. pmc Genetic labeling does not detect epithelial-to-mesenchymal transition of cholangiocytes in liver fibrosis in mice
    David Scholten
    Department of Medicine, University of California, San Diego, La Jolla, California, USA
    Gastroenterology 139:987-98. 2010
    ....
  12. pmc Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice
    Fanli Meng
    Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, California, USA
    Gastroenterology 143:765-76.e1-3. 2012
    ..Interleukin (IL)-17 signaling has been implicated in lung and skin fibrosis. We examined the role of IL-17 signaling in the pathogenesis of liver fibrosis in mice...
  13. 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...
  14. 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
    ....
  15. 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...
  16. ncbi request reprint Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice
    Liu Yang
    Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
    J Hepatol 43:317-23. 2005
    ..Pharmacological blockade of the renin-angiotensin system (RAS) attenuates liver fibrogenesis in rats. Here, we provide genetic evidence implicating angiotensin type 1 (AT1) receptors in liver fibrogenesis...
  17. 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...
  18. 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...
  19. 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...
  20. ncbi request reprint Roles for C16-ceramide and sphingosine 1-phosphate in regulating hepatocyte apoptosis in response to tumor necrosis factor-alpha
    Yosuke Osawa
    Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA
    J Biol Chem 280:27879-87. 2005
    ..NCDase prevented apoptosis both by reducing C16-ceramide and by activation of AKT through S1P formation. Therefore, the cross-talk between sphingolipids and AKT pathway may determine hepatocyte apoptosis by TNF-alpha...
  21. 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...
  22. ncbi request reprint Differential requirement for c-Jun NH2-terminal kinase in TNFalpha- and Fas-mediated apoptosis in hepatocytes
    Robert F Schwabe
    Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
    FASEB J 18:720-2. 2004
    ..This study demonstrates that JNK augments TNF-alpha-induced apoptosis in hepatocytes through a signaling pathway that is distinct from the pathway by which it regulates proliferation...
  23. pmc Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver
    Christoph H Osterreicher
    Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 108:308-13. 2011
    ..These findings suggest that FSP1 is a marker of a specific subset of inflammatory macrophages in liver injury, fibrosis, and cancer...
  24. doi request reprint Antiapoptotic effect of c-Jun N-terminal Kinase-1 through Mcl-1 stabilization in TNF-induced hepatocyte apoptosis
    Yuzo Kodama
    Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA
    Gastroenterology 136:1423-34. 2009
    ..Although myeloid cell leukemia-1 (Mcl-1) has been reported as a substrate of JNK, the role of Mcl-1 and its functional regulation by JNK in TNF-induced hepatocyte apoptosis and liver injury remain to be elucidated...
  25. pmc The enteropathy of prostaglandin deficiency
    David H Adler
    Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Vanderbilt Medical Center, 1211 Medical Center Drive, Nashville, TN 37232, USA
    J Gastroenterol 44:1-7. 2009
    ..We present here a genetic deficiency of eicosanoid biosynthesis that illuminates the mechanism of NSAID-induced ulcers of the small intestine...
  26. ncbi request reprint A dual reporter gene transgenic mouse demonstrates heterogeneity in hepatic fibrogenic cell populations
    Scott T Magness
    University of North Carolina at Chapel Hill, Department of Medicine, USA
    Hepatology 40:1151-9. 2004
    ..These reporter mice provide a useful tool to further characterize fibrogenic cell types and to evaluate antifibrotic drugs...
  27. pmc 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...
  28. ncbi request reprint In vivo pattern of lipopolysaccharide and anti-CD3-induced NF-kappa B activation using a novel gene-targeted enhanced GFP reporter gene mouse
    Scott T Magness
    Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    J Immunol 173:1561-70. 2004
    ..In summary, the cis-NF-kappa B(EGFP) mouse will serve as a valuable tool to address multiple questions regarding the cell-specific and real-time activation of NF-kappa B during normal and diseased states...
  29. ncbi request reprint DNase I-hypersensitive sites enhance alpha1(I) collagen gene expression in hepatic stellate cells
    Yutaka Yata
    Department of Medicine, The University of North Carolina at Chapel Hill, 27599, USA
    Hepatology 37:267-76. 2003
    ..The collagen-GFP transgenic mice provide a convenient and reliable model system to investigate the molecular mechanisms controlling increased collagen expression during fibrosis...
  30. pmc Hepatocytes do not undergo epithelial-mesenchymal transition in liver fibrosis in mice
    Kojiro Taura
    Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, CA, USA
    Hepatology 51:1027-36. 2010
    ..In liver sections of CCl(4)-treated mice, GFP-positive areas were coincident with fibrotic septa and never overlapped X-gal-positive areas...
  31. ncbi request reprint Anandamide induces necrosis in primary hepatic stellate cells
    Soren V Siegmund
    Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA
    Hepatology 41:1085-95. 2005
    ..The anti-proliferative effects and the selective killing of HSCs, but not hepatocytes, indicate that AEA may be used as a potential anti-fibrogenic tool...
  32. ncbi request reprint JNK mediates hepatic ischemia reperfusion injury
    Tetsuya Uehara
    Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    J Hepatol 42:850-9. 2005
    ..The aim of this study is to assess the role of JNK during warm I/R injury using novel selective JNK inhibitors...
  33. ncbi request reprint Human hepatic stellate cells express CCR5 and RANTES to induce proliferation and migration
    Robert F Schwabe
    Columbia University College of Physicians and Surgeons, 630 West 168th St, PH8East, Rm 105J, New York, NY 10032 3784, USA
    Am J Physiol Gastrointest Liver Physiol 285:G949-58. 2003
    ..In conclusion, RANTES and CCR5 represent potential mediators of 1) HSC migration and proliferation and 2) a cross-talk between HSCs and leukocytes during fibrogenesis...
  34. ncbi request reprint Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells
    Yong Han Paik
    Department of Medicine, University of North Carolina at Chapel Hill, USA
    Hepatology 37:1043-55. 2003
    ..In conclusion, human activated HSCs utilize components of TLR4 signal transduction cascade to stimulate NF-kappaB and JNK and up-regulate chemokines and adhesion molecules. Thus, HSCs are a potential mediator of LPS-induced liver injury...
  35. 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...
  36. ncbi request reprint Systemic infusion of angiotensin II exacerbates liver fibrosis in bile duct-ligated rats
    Ramon Bataller
    Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7038, USA
    Hepatology 41:1046-55. 2005
    ..In conclusion, increased systemic Ang II augments hepatic fibrosis and promotes inflammation, oxidative stress, and thrombogenic events...
  37. 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
    ....
  38. pmc Toll-like receptor 2-mediated intestinal injury and enteric tumor necrosis factor receptor I contribute to liver fibrosis in mice
    Phillipp Hartmann
    Department of Medicine, University of California San Diego, La Jolla, California 92093, USA
    Gastroenterology 143:1330-40.e1. 2012
    ..We used a mouse model of cholestatic liver disease to investigate mechanisms of intestinal barrier disruption following liver injury...
  39. 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
    ....
  40. ncbi request reprint Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver
    Yosuke Osawa
    Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA
    Hepatology 42:1320-8. 2005
    ..In conclusion, BDL exerts antiapoptotic effects that appear to require activation of AKT in hepatocytes and SphK in HSCs...
  41. doi request reprint Hepatitis C virus-induced oxidative stress suppresses hepcidin expression through increased histone deacetylase activity
    Kouichi Miura
    Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
    Hepatology 48:1420-9. 2008
    ..In addition, an HDAC inhibitor restored their binding to the hepcidin promoter via acetylation of histones...
  42. ncbi request reprint Gliotoxin-mediated apoptosis of activated human hepatic stellate cells
    Young Oh Kweon
    Division of Digestive Diseases and Nutrition, Department of Medicine, CB 7038, Glaxo Research Bldg Rm 156, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    J Hepatol 39:38-46. 2003
    ..Gliotoxin induces apoptosis of activated human and rat HSCs by an unknown mechanism...
  43. ncbi request reprint Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis
    Tatiana Kisseleva
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    J Hepatol 45:429-38. 2006
    ..Hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis. However, their origin is still unknown. We tested the hypothesis that bone marrow (BM) contributes to the population of HSCs...
  44. pmc Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent
    Tomonori Aoyama
    Department of Medicine, University of California San Diego, La Jolla, CA 92093 0602, USA
    Hepatology 56:2316-27. 2012
    ..Treatment with GKT137831 suppressed ROS production and NOX and fibrotic gene expression, but not Rac1 activity, in SOD1mut and WT HSCs. Both Ang II and tumor growth factor beta up-regulated NOX4, but Ang II required NOX1...
  45. pmc Fibrogenesis of parenchymal organs
    Tatiana Kisseleva
    Department of Medicine, University of California, San Diego, La Jolla, California, USA
    Proc Am Thorac Soc 5:338-42. 2008
    ..These concepts open new prospects for multidisciplinary research and the development of new therapies for fibrosis...
  46. ncbi request reprint Prolonged infusion of angiotensin II into normal rats induces stellate cell activation and proinflammatory events in liver
    Ramon Bataller
    Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7032, USA
    Am J Physiol Gastrointest Liver Physiol 285:G642-51. 2003
    ..In conclusion, increased systemic ANG II can induce liver injury by promoting proinflammatory events and vascular damage. ANG II-induced hepatic effects are not dependent on increase in arterial pressure...
  47. 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...
  48. ncbi request reprint Molecular pathogenesis of alcohol-induced hepatic fibrosis
    Soren V Siegmund
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Alcohol Clin Exp Res 29:102S-109S. 2005
    ..These new results in basic science are encouraging for the search of new antifibrotic treatment...
  49. pmc Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis
    Tatiana Kisseleva
    Department of Medicine, School of Pharmacy, University of California, San Diego, CA 92093, USA
    Proc Natl Acad Sci U S A 109:9448-53. 2012
    ..Inactivation of HSCs was associated with up-regulation of the anti-apoptotic genes Hspa1a/b, which participate in the survival of HSCs in culture and in vivo...
  50. ncbi request reprint Molecular mechanisms of alcohol-induced hepatic fibrosis
    Soren V Siegmund
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Dig Dis 23:264-74. 2005
    ....
  51. pmc Protection from liver fibrosis by a peroxisome proliferator-activated receptor δ agonist
    Keiko Iwaisako
    Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 109:E1369-76. 2012
    ....
  52. pmc What's new in liver fibrosis? The origin of myofibroblasts in liver fibrosis
    Keiko Iwaisako
    Department of Medicine, University of California, San Diego, La Jolla, California 92093 0602, USA
    J Gastroenterol Hepatol 27:65-8. 2012
    ..It is suggested that hepatic injury of different etiology triggers the transdifferentiation to myofibroblasts from distinct cell populations. Here we discuss the origin and fate of myofibroblast in liver fibrosis...
  53. ncbi request reprint Free cholesterol-loaded macrophages are an abundant source of tumor necrosis factor-alpha and interleukin-6: model of NF-kappaB- and map kinase-dependent inflammation in advanced atherosclerosis
    Yankun Li
    Department of Medicine, Columbia University, 630 West 168th Street, New York, NY 10032, USA
    J Biol Chem 280:21763-72. 2005
    ..Moreover, this model may help explain the relationship between FC accumulation and inflammation in vulnerable plaques...
  54. 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...
  55. ncbi request reprint c-Jun N-terminal kinase mediates hepatic injury after rat liver transplantation
    Tetsuya Uehara
    Department of Medicine, University of North Carolina at Chapel Hill, USA
    Transplantation 78:324-32. 2004
    ..Although c-Jun N-terminal kinase (JNK) is rapidly activated after OLT, the functional consequences of JNK activation are unknown. The aim of this study was to address the role of JNK after OLT using the selective JNK inhibitor CC-401...
  56. 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
    ....
  57. ncbi request reprint c-Jun-N-terminal kinase drives cyclin D1 expression and proliferation during liver regeneration
    Robert F Schwabe
    Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Hepatology 37:824-32. 2003
    ..In conclusion, our data show that JNK drives G0 to G1 transition in hepatocytes and that cyclin D1 is a downstream target of the JNK pathway during liver regeneration...
  58. ncbi request reprint NADPH oxidase in the liver: defensive, offensive, or fibrogenic?
    Samuele De Minicis
    Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA
    Gastroenterology 131:272-5. 2006
  59. 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...
  60. ncbi request reprint The genetics of nonalcoholic fatty liver disease
    Christoph H Osterreicher
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093 0602, USA
    Ann Hepatol 6:83-8. 2007
    ..The present review article summarizes currently available data from genotype-phenotype studies and defines candidate genes that deserve future investigation...
  61. pmc Genetic covariance between gamma-glutamyl transpeptidase and fatty liver risk factors: role of beta2-adrenergic receptor genetic variation in twins
    Rohit Loomba
    Department of Medicine, University of California at San Diego, La Jolla, California, USA
    Gastroenterology 139:836-45, 845.e1. 2010
    ..We estimated the heritability of GGT using a twin-study design and examined the genetic covariance between GGT levels, IR, hypertension, levels of low-density lipoproteins and triglycerides, and ADRB2 variants...
  62. 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...
  63. ncbi request reprint Role of hepatic stellate cells in fibrogenesis and the reversal of fibrosis
    Tatiana Kisseleva
    Department of Medicine, Columbia University, New York, USA
    J Gastroenterol Hepatol 22:S73-8. 2007
    ..This review is focused on recent progress in the study of the pathogenesis of liver fibrosis...
  64. pmc NOX in liver fibrosis
    Samuele De Minicis
    Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10026, USA
    Arch Biochem Biophys 462:266-72. 2007
    ..In addition to the p47(phox) component, only Rac1 has been identified as a functional active component of the NADPH oxidase complex in HSCs...
  65. ncbi request reprint Hepatic stellate cells and the reversal of fibrosis
    Tatiana Kisseleva
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    J Gastroenterol Hepatol 21:S84-7. 2006
    ..Thus, HSC represent an appealing target for antifibrotic therapy. This review will focus on some aspects of etiology and molecular pathogenesis of liver fibrosis and the reversal of fibrosis...
  66. doi request reprint High molecular weight adiponectin inhibits proliferation of hepatic stellate cells via activation of adenosine monophosphate-activated protein kinase
    Masayuki Adachi
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Hepatology 47:677-85. 2008
    ....
  67. ncbi request reprint Mechanisms of Liver Injury. I. TNF-alpha-induced liver injury: role of IKK, JNK, and ROS pathways
    Robert F Schwabe
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Am J Physiol Gastrointest Liver Physiol 290:G583-9. 2006
    ..In light of recent findings, pharmacological inhibitors of JNK and IKK and antioxidants may be promising new tools for the treatment of hepatitis, ischemia-reperfusion injury, and hepatocellular carcinoma...
  68. 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
  69. ncbi request reprint The role of focal adhesion kinase-phosphatidylinositol 3-kinase-akt signaling in hepatic stellate cell proliferation and type I collagen expression
    Shimon Reif
    Division of Digestive Diseases, Department of Medicine, University of North Carolina, Chapel Hill 27599, USA
    J Biol Chem 278:8083-90. 2003
    ..PI3K is positioned downstream of FAK. Signals for HSC proliferation are transduced through FAK, PI3K, and Akt. Finally, expression of type I collagen is regulated by the PI3K-Akt signaling pathway...
  70. doi request reprint Mechanisms of fibrogenesis
    Tatiana Kisseleva
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093 0602, USA
    Exp Biol Med (Maywood) 233:109-22. 2008
    ....
  71. doi request reprint Oxidative stress in alcoholic liver disease: role of NADPH oxidase complex
    Samuele De Minicis
    UCSD School of Medicine, Department of Medicine, La Jolla, California 92093 0602, USA
    J Gastroenterol Hepatol 23:S98-103. 2008
    ..NADPH oxidase is expressed in hepatocytes, hepatic stellate cells and Kupffer cells in the liver. Studying NADPH oxidase gives new insights into alcohol-induced liver damage and provides new direction for future therapeutic strategies...
  72. ncbi request reprint Clinical syndromes of alcoholic liver disease
    Masayuki Adachi
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Dig Dis 23:255-63. 2005
    ..To understand the clinical syndromes of alcoholic liver disease, this review highlights the papers on both clinical and basic research of alcoholic liver disease, especially on steatosis, alcoholic hepatitis and fibrosis...
  73. pmc Anti-fibrogenic strategies and the regression of fibrosis
    Tatiana Kisseleva
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093 0602, USA
    Best Pract Res Clin Gastroenterol 25:305-17. 2011
    ..Here we discuss the origin of activated myofibroblasts and different aspects of their activation, differentiation and potential inactivation during regression of liver fibrosis...
  74. ncbi request reprint TRAIL-mediated apoptosis requires NF-kappaB inhibition and the mitochondrial permeability transition in human hepatoma cells
    Young Soo Kim
    Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
    Hepatology 36:1498-508. 2002
    ..Inhibition of NF-kappaB unmasks a TRAIL-induced apoptotic signaling cascade that involves FADD, caspase 8, the MPT, and caspase 3...
  75. ncbi request reprint Zinc finger protein 267 is up-regulated during the activation process of human hepatic stellate cells and functions as a negative transcriptional regulator of MMP-10
    Bernd Schnabl
    Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
    Biochem Biophys Res Commun 335:87-96. 2005
    ..In conclusion, our results suggest that ZNF267 as a negative transcriptional regulator of MMP-10 might promote liver fibrogenesis through alteration of matrix degradation in vivo...
  76. ncbi request reprint Role of glycogen synthase kinase-3 in TNF-alpha-induced NF-kappaB activation and apoptosis in hepatocytes
    Robert F Schwabe
    Department of Medicine, Biochemistry, and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Am J Physiol Gastrointest Liver Physiol 283:G204-11. 2002
    ..These results indicate that GSK-3 protects hepatocytes from TNF-alpha-induced apoptosis through p65 phosphorylation and upregulation of NF-kappaB transactivation...
  77. ncbi request reprint Genetic polymorphisms and the progression of liver fibrosis: a critical appraisal
    Ramon Bataller
    Department of Medicine, Biochemistry and Biophysics, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC 27599, USA
    Hepatology 37:493-503. 2003
    ..Large-scale, well-designed studies are required to clarify the actual role of this factor and other genetic variants in liver fibrosis...
  78. ncbi request reprint Inhibition of collagen alpha 1(I) expression by the 5' stem-loop as a molecular decoy
    Branko Stefanovic
    Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 277:18229-37. 2002
    ..The molecular decoys provide a generalized method of assessing the functional significance of blocking the interactions of mRNA and proteins...
  79. ncbi request reprint Liver fibrosis: signals leading to the amplification of the fibrogenic hepatic stellate cell
    Erwin Gabele
    Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Front Biosci 8:d69-77. 2003
    ..The discussion will include collagen gene regulation and proliferative signals that contribute to the amplification of the hepatic stellate cell, the primary fibrogenic cell type that resides in the liver...
  80. ncbi request reprint Genomics of liver fibrosis and cirrhosis
    Christoph H Osterreicher
    Department of Medicine, Division of Digestive and Liver Diseases, Columbia University, New York, New York 10032, USA
    Semin Liver Dis 27:28-43. 2007
    ....
  81. ncbi request reprint An exon 10 deletion in the mouse ferrochelatase gene has a dominant-negative effect and causes mild protoporphyria
    Scott T Magness
    Department of Medicine, University of North Carolina at Chapel Hill 27599, USA
    Blood 100:1470-7. 2002
    ..Heterozygous mice exhibited skin photosensitivity but no liver disease. These results lend support for a dominant-negative effect of a mutant allele on ferrochelatase activity in patients with protoporphyria...
  82. ncbi request reprint Liver fibrogenesis: a new role for the renin-angiotensin system
    Ramon Bataller
    Institut de Malalties Digestives i Metaboliques, Hospital Clinic, IDIBAPS, Barcelona, Catalonia, Spain
    Antioxid Redox Signal 7:1346-55. 2005
    ..Although no prospective studies have evaluated the antifibrotic effect of RAS inhibitors in patients with chronic liver diseases, controlled clinical trials are under way...
  83. ncbi request reprint Expression of the NF-kappa B target gene X-ray-inducible immediate early response factor-1 short enhances TNF-alpha-induced hepatocyte apoptosis by inhibiting Akt activation
    Yosuke Osawa
    First Department of Internal Medicine, Gifu University School of Medicine, Tsukasamachi, Gifu, Japan
    J Immunol 170:4053-60. 2003
    ..Moreover, the reciprocal cross-talk between IEX-1S and PI3K/Akt may closely be involved in the regulation of TNF-alpha-induced hepatocyte apoptosis...
  84. ncbi request reprint Epimorphin, a morphogenic protein, induces proteases in rodent hepatocytes through NF-kappaB
    Kouichi Miura
    Department of Gastroenterology, Akita University School of Medicine, 1 1 1 Hondo, Akita 010 8543, Japan
    J Hepatol 47:834-43. 2007
    ..Epimorphin, expressed by hepatic stellate cells in the liver, directs normal morphogenesis in various organs. The aim of this study was to clarify the mechanism by which epimorphin functions as a morphogen in vitro...
  85. ncbi request reprint Up-regulated eotaxin plasma levels in chronic liver disease patients indicate hepatic inflammation, advanced fibrosis and adverse clinical course
    Frank Tacke
    Medical Clinic III, University Hospital Aachen, Aachen, Germany
    J Gastroenterol Hepatol 22:1256-64. 2007
    ..The aim of this study was to analyze the role of eotaxin in chronic liver disease...
  86. ncbi request reprint Hepatic stellate cells primed with cytokines upregulate inflammation in response to peptidoglycan or lipoteichoic acid
    Yong Han Paik
    Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
    Lab Invest 86:676-86. 2006
    ..5). These findings suggest that TNF-alpha or IL-1beta primed HSCs enhance the production of IL-8 in response to PGN and LTA through augmentation of the TLR2 system...
  87. ncbi request reprint Delivery of matrix metalloproteinase-1 attenuates established liver fibrosis in the rat
    Yuji Iimuro
    Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Japan
    Gastroenterology 124:445-58. 2003
    ....
  88. ncbi request reprint Nuclear factor-kappaB in the liver: friend or foe?
    Robert F Schwabe
    Gastroenterology 132:2601-4. 2007
  89. ncbi request reprint Norepinephrine induces calcium spikes and proinflammatory actions in human hepatic stellate cells
    Pau Sancho-Bru
    Liver Unit, Institut Clinic de Malalties Digestives i Metaboliques, Hospital Clinic, Villarroel 170, Barcelona, Spain
    Am J Physiol Gastrointest Liver Physiol 291:G877-84. 2006
    ..We conclude that NE stimulates NF-kappaB and induces cell contraction and proinflammatory effects in human HSC. Catecholamines may participate in the pathogenesis of portal hypertension and liver fibrosis by targeting HSC...
  90. ncbi request reprint From quiescence to activation: Gene regulation in hepatic stellate cells
    Richard A Rippe
    Gastroenterology 127:1260-2. 2004
  91. ncbi request reprint Transforming growth factor-beta1 induces hepatocyte apoptosis by a c-Jun independent mechanism
    Charles M Samson
    Department of Surgery, The University of North Carolina, Chapel Hill 27599, USA
    Surgery 132:441-9. 2002
    ..We hypothesized that autocrine expression of activated TGF-beta1 (Ad5aTGF-beta1) would increase c-jun expression in rat liver and limit hepatic regeneration by inducing apoptosis...
  92. ncbi request reprint Liver regeneration is suppressed in small-for-size liver grafts after transplantation: involvement of c-Jun N-terminal kinase, cyclin D1, and defective energy supply
    Zhi Zhong
    Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, 29425, USA
    Transplantation 82:241-50. 2006
    ..Small-for-size liver grafts have decreased survival compared to full-size grafts. This study investigated mechanisms of suppression of liver regeneration in small-for-size grafts...
  93. ncbi request reprint Jun kinase modulates tumor necrosis factor-dependent apoptosis in liver cells
    Christian Liedtke
    Department of Gastroenterology and Hepatology, Medizinische Hochschule Hannover, Hannover Germany
    Hepatology 36:315-25. 2002
    ....
  94. ncbi request reprint Bone morphogenetic protein 7 is elevated in patients with chronic liver disease and exerts fibrogenic effects on human hepatic stellate cells
    Frank Tacke
    Medical Clinic III, University Hospital Aachen, Aachen, Germany
    Dig Dis Sci 52:3404-15. 2007
    ..Elevated systemic and hepatic levels of BMP7 in patients with chronic liver disease may contribute to progression of liver fibrogenesis in vivo...
  95. ncbi request reprint Salicylate enhances necrosis and apoptosis mediated by the mitochondrial permeability transition
    Ki Wan Oh
    Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, 27599, USA
    Toxicol Sci 73:44-52. 2003
    ..Enhancement by salicylate of MPT-dependent apoptosis may play a role in protection by aspirin and other nonsteroidal anti-inflammatory drugs against colon, lung, and breast cancer...
  96. ncbi request reprint NF-kappaB activation in Kupffer cells after partial hepatectomy
    Liu Yang
    Dept of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
    Am J Physiol Gastrointest Liver Physiol 289:G530-8. 2005
    ..During liver regeneration, EGFP expression was detected within 12 h and was primarily located in Kupffer cells. Our data demonstrate that activation of NF-kappaB initially occurs in Kupffer cells after partial hepatectomy in mice...
  97. pmc Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury
    Tom Luedde
    Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
    J Clin Invest 115:849-59. 2005
    ....
  98. pmc Liver fibrosis
    Ramon Bataller
    Liver Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clinic, Institut d Investigació Biomèdiques August Pi i Sunyer IDIBAPS, Barcelona, Catalonia, Spain
    J Clin Invest 115:209-18. 2005
    ..This review summarizes recent progress in the study of the pathogenesis and diagnosis of liver fibrosis and discusses current antifibrotic strategies...
  99. ncbi request reprint Akt activation protects rat liver from ischemia/reperfusion injury
    Nobuko Harada
    Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
    J Surg Res 121:159-70. 2004
    ..Akt, a serine-threonine protein kinase, is known to promote cell survival. We investigated whether gene transfer of constitutively active or dominant negative Akt could affect hepatic I/R injury...
  100. ncbi request reprint Lipopolysaccharide-binding protein modulates hepatic damage and the inflammatory response after hemorrhagic shock and resuscitation
    Mark Lehnert
    Medical Univ of South Carolina, 280 Calhoun St, PO Box 250140, Charleston, SC 29425, USA
    Am J Physiol Gastrointest Liver Physiol 291:G456-63. 2006
    ..An absence of LBP blunts hepatocellular injury with decreased neutrophil infiltration, oxidative stress, and c-Jun and ERK activation...
  101. ncbi request reprint Antifibrotic effects of a tissue inhibitor of metalloproteinase-1 antibody on established liver fibrosis in rats
    Christopher J Parsons
    Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, USA
    Hepatology 40:1106-15. 2004
    ..Zymography analysis showed antibody treatment decreased the activity of MMP-2. In conclusion, administration of a TIMP-1 antibody attenuated CCl(4)-induced liver fibrosis and decreased HSC activation and MMP-2 activity...