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This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically(More)
Primary hepatocyte cell cultures are widely used for studying hepatic diseases with alterations in hepatic glucose and lipid metabolism, such as diabetes and non-alcoholic fatty liver disease. Therefore, small interfering RNAs (siRNAs) provide a potent and specific tool to elucidate the signaling pathways and gene functions involved in these pathologies.(More)
Hedgehog signaling plays an important role in embryonic development, organogenesis and cancer. In the adult liver, Hedgehog signaling in non-parenchymal cells has been found to play a role in certain disease states such as fibrosis and cirrhosis. However, whether the Hedgehog pathway is active in mature healthy hepatocytes and is of significance to liver(More)
Network inference is an important tool to reveal the underlying interactions of biological systems. In the liver, a complex system of transcription factors is active to distribute signals and induce the cellular response following extracellular stimuli. Plenty of information is available about single transcription factors important for the different(More)
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in industrialized countries and is increasing in prevalence. The pathomechanisms, however, are poorly understood. This study assessed the unexpected role of the Hedgehog pathway in adult liver lipid metabolism. Using transgenic mice with conditional hepatocyte-specific deletion of(More)
The GLI transcription factors, GLI1, GLI2, and GLI3, transduce Hedgehog and non-hedgehog signals and are involved in regulating development and tumorgenesis. Surprisingly, they were recently found to modulate important functions of mature liver. However, less is known about their mutual interactions and possible target genes in mature hepatocytes. To get a(More)
systems available that is valued for its simple applicability, both in vitro and in vivo (Bozzuto and Molinari 2015). Among the few drawbacks of liposomes, cytotoxic-ity and immunomodulation have attracted most attention and many studies have been performed to minimise such adverse effects (Battaglia and Gallarate 2012; Peer 2012). At the sub-toxic level,(More)
Development of mice with hepatocyte knockout of lanosterol 14α-demethylase (HCyp51-/-) from cholesterol synthesis is characterized by the progressive onset of liver injury with ductular reaction and fibrosis. These changes begin during puberty and are generally more aggravated in the knockout females. However, a subgroup of (pre)pubertal knockout mice(More)
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