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Liver-specific Gene Expression (liver-specific + gene_expression)

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Medical Sciences100%

Selected Abstracts

Transcription factor HNF and hepatocyte differentiation

HEPATOLOGY RESEARCH, Issue 10 2008
Masahito Nagaki
To know the precise mechanisms underlying the life or death and the regeneration or differentiation of cells would be relevant and useful for the development of a regenerative therapy for organ failure. Liver-specific gene expression is controlled primarily at a transcriptional level. Studies on the transcriptional regulatory elements of genes expressed in hepatocytes have identified several liver-enriched transcriptional factors, including hepatocyte nuclear factor (HNF)-1, HNF-3, HNF-4, HNF-6 and CCAAT/enhancer binding protein families, which are key components of the differentiation process for the fully functional liver. The transcriptional regulation by these HNFs, which form a hierarchical and cooperative network, is both essential for hepatocyte differentiation during mammalian liver development and also crucial for metabolic regulation and liver function. Among these liver-enriched transcription factors, HNF-4 is likely to act the furthest upstream as a master gene in transcriptional cascade and interacts with other liver-enriched transcriptional factors to stimulate hepatocyte-specific gene transcription. A link between the extracellular matrix, changes in cytoskeletal filament assembly and hepatocyte differentiation via HNF-4 has been shown to be involved in the transcriptional regulation of liver-specific gene expression. This review provides an overview of the roles of liver-enriched transcription factors in liver function. [source]

Gap junction-mediated intercellular communication in a long-term primary mouse hepatocyte culture system

HEPATOLOGY, Issue 5 2003
Stephanie A. Stoehr
Gap junction-mediated intercellular communication (GJIC) is critical for maintaining integral cellular processes including differentiation and growth control. The disruption of GJIC has been correlated with aberrant function in many cell types, including hepatocytes in vivo; therefore it is imperative that cellular model systems support intercellular communication to simulate normal cellular functions. Functional GJIC has been shown in long-term primary rat hepatocyte cultures, which have been implemented widely to study various aspects of hepatocellular function; however, the onset of transgenic technology in murine species has necessitated the development of a primary mouse hepatocyte system. In this report, we analyze GJIC in a dimethylsulfoxide (DMSO)-containing long-term primary mouse hepatocyte culture system. The cells retain morphologic and biochemical characteristics of differentiated hepatocytes through day 30 post plating, including liver-specific gene expression. We further show that connexin32 and connexin26 expression and gap junction plaque formation increase over time in culture concomitant with an increase in GJIC between adjoining primary mouse hepatocytes. In conclusion, the findings described in this study make it possible to maintain differentiated primary mouse hepatocytes that also show GJIC in long-term culture for 30 days. In addition, this system has the potential to be extended to study primary mouse hepatocytes isolated from genetically engineered mice. [source]

Transcription factor HNF and hepatocyte differentiation

HEPATOLOGY RESEARCH, Issue 10 2008
Masahito Nagaki
To know the precise mechanisms underlying the life or death and the regeneration or differentiation of cells would be relevant and useful for the development of a regenerative therapy for organ failure. Liver-specific gene expression is controlled primarily at a transcriptional level. Studies on the transcriptional regulatory elements of genes expressed in hepatocytes have identified several liver-enriched transcriptional factors, including hepatocyte nuclear factor (HNF)-1, HNF-3, HNF-4, HNF-6 and CCAAT/enhancer binding protein families, which are key components of the differentiation process for the fully functional liver. The transcriptional regulation by these HNFs, which form a hierarchical and cooperative network, is both essential for hepatocyte differentiation during mammalian liver development and also crucial for metabolic regulation and liver function. Among these liver-enriched transcription factors, HNF-4 is likely to act the furthest upstream as a master gene in transcriptional cascade and interacts with other liver-enriched transcriptional factors to stimulate hepatocyte-specific gene transcription. A link between the extracellular matrix, changes in cytoskeletal filament assembly and hepatocyte differentiation via HNF-4 has been shown to be involved in the transcriptional regulation of liver-specific gene expression. This review provides an overview of the roles of liver-enriched transcription factors in liver function. [source]

Characterization of a Hollow Fiber Bioartificial Liver Device

ARTIFICIAL ORGANS, Issue 5 2005
Susan Fugett Abu-Absi
Abstract:, A three-compartment bioartificial liver (BAL) has been developed for potential treatment of fulminant hepatic failure. It has been shown previously that viability and liver-specific functions were maintained in laboratory-scale bioreactors of such design. In this study, the performance of hepatocytes in a clinical-scale bioartificial liver was verified by sustained specific production rates of albumin and urea, along with oxygen consumption rates for up to 56 h and liver-specific gene expression for up to 72 h. In addition, transmission of porcine endogenous retrovirus and other type C retroviral particles across the hollow fibers was not detected under both normal and extreme operating fluxes. These results demonstrate that the clinical-scale BAL performs at a level similar to the laboratory scale ,and, that, it, offers, a, viral, barrier, against, porcine , retroviruses. [source]