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Hepatocyte autotaxin expression promotes liver fibrosis and cancer

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Autor
Kaffe E., Katsifa A., Xylourgidis N., Ninou I., Zannikou M., Harokopos V., Foka P., Dimitriadis A., Evangelou K., Moulas A.N., Georgopoulou U., Gorgoulis V.G., Dalekos G.N., Aidinis V.
Fecha
2017
Language
en
DOI
10.1002/hep.28973
Materia
autotaxin
carbon tetrachloride
growth factor
lysophosphatidic acid
lysophospholipase
lysophospholipid
6-(3-(piperazin-1-yl)propanoyl)benzo(d)oxazol-2(3H)-one
alkylglycerophosphoethanolamine phosphodiesterase
benzoxazole derivative
phosphodiesterase
piperazine derivative
animal experiment
animal model
animal tissue
Article
chronic liver disease
controlled study
deregulation
electrospray mass spectrometry
enzyme linked immunosorbent assay
female
gene deletion
gene overexpression
hepatic stellate cell
hepatitis C
high performance liquid chromatography
human
lipid homeostasis
liver cancer
liver cell carcinoma
liver cirrhosis
liver fibrosis
liver histology
liver toxicity
male
mouse
nonhuman
overall survival
protein expression
real time polymerase chain reaction
RNA extraction
Western blotting
animal
C57BL mouse
case control study
cell culture
chronic disease
cytology
disease course
disease model
drug effects
genetics
immunohistochemistry
liver cell
liver tumor
metabolism
molecularly targeted therapy
needle biopsy
pathology
Animals
Benzoxazoles
Biopsy, Needle
Carcinoma, Hepatocellular
Case-Control Studies
Cells, Cultured
Chronic Disease
Disease Models, Animal
Disease Progression
Gene Deletion
Hepatocytes
Humans
Immunohistochemistry
Liver Cirrhosis
Liver Neoplasms
Mice
Mice, Inbred C57BL
Molecular Targeted Therapy
Phosphoric Diester Hydrolases
Piperazines
John Wiley and Sons Inc.
Mostrar el registro completo del ítem
Resumen
Autotaxin (ATX) is a secreted lysophospholipase D that catalyzes the production of lysophosphatidic acid (LPA), a pleiotropic growth-factor–like lysophospholipid. Increased ATX expression has been detected in various chronic inflammatory disorders and different types of cancer; however, little is known about its role and mode of action in liver fibrosis and cancer. Here, increased ATX expression was detected in chronic liver disease (CLD) patients of different etiologies, associated with shorter overall survival. In mice, different hepatotoxic stimuli linked with the development of different forms of CLDs were shown to stimulate hepatocyte ATX expression, leading to increased LPA levels, activation of hepatic stellate cells (HSCs), and amplification of profibrotic signals. Hepatocyte-specific, conditional genetic deletion and/or transgenic overexpression of ATX established a liver profibrotic role for ATX/LPA, whereas pharmacological ATX inhibition studies suggested ATX as a possible therapeutic target in CLDs. In addition, hepatocyte ATX ablation and the consequent deregulation of lipid homeostasis was also shown to attenuate hepatocellular carcinoma (HCC) development, thus implicating ATX/LPA in the causative link of cirrhosis and HCC. Conclusion: ATX is a novel player in the pathogenesis of liver fibrosis and cancer and a promising therapeutic target. (Hepatology 2017;65:1369-1383). © 2016 by the American Association for the Study of Liver Diseases.
URI
http://hdl.handle.net/11615/74137
Colecciones
  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ. [19735]

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