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Functional Liver (functional + liver)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Mutation in the abcb7 gene causes abnormal iron and fatty acid metabolism in developing medaka fish

DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 9 2008
Akimitsu Miyake
The medaka fish (Oryzias latipes) is an emerging model organism for which a variety of unique developmental mutants have now been generated. Our recent mutagenesis screening of the medaka isolated a unique mutant that develops a fatty liver at larval stages. Positional cloning identified the responsible gene as medaka abcb7. Abcb7, a mitochondrial ABC (ATP binding cassette) half-transporter, has been implicated in iron metabolism. Recently, human Abcb7 was found to be mutated in X-linked sideroblastic anemia with cerebellar ataxia (XLSA/A). The homozygous medaka mutant exhibits abnormal iron metabolism in erythrocytes and accumulation of lipid in the liver. Microarray and in situ hybridization analyses demonstrated that the expression of genes involved in iron and lipid metabolisms are both affected in the mutant liver, suggesting novel roles of Abcb7 in the development of physiologically functional liver. The medaka abcb7 mutant thus could provide insights into the pathogenesis of XLSA/A as well as the normal function of the gene. [source]

New school in liver development: Lessons from zebrafish,

HEPATOLOGY, Issue 5 2009
Jaime Chu
There is significant overlap in the genes and pathways that control liver development and those that regulate liver regeneration, hepatic progenitor cell expansion, response to injury, and cancer. Additionally, defects in liver development may underlie some congenital and perinatal liver diseases. Thus, studying hepatogenesis is important for understanding not only how the liver forms, but also how it functions. Elegant work in mice has uncovered a host of transcription factors and signaling molecules that govern the early steps of hepatic specification; however, the inherent difficulty of studying embryogenesis in utero has driven developmental biologists to seek new systems. The rapidly developing vertebrate zebrafish is a favorite model for embryology. The power of forward genetic screens combined with live real-time imaging of development in transparent zebrafish embryos has highlighted conserved processes essential for hepatogenesis and has uncovered some exciting new players. This review presents the advantages of zebrafish for studying liver development, underscoring how studies in zebrafish and mice complement each other. In addition to their value for studying development, zebrafish models of hepatic and biliary diseases are expanding, and using these small, inexpensive embryos for drug screening has become de rigueur. Zebrafish provide a shared platform for developmental biology and translational research, offering innovative methods for studying liver development and disease. The story of hepatogenesis has something for everyone. It involves transcriptional regulation, cell-cell interaction, signaling pathways, control of cell proliferation and apoptosis, plus morphogenic processes that sculpt vasculature, parenchymal cells, and mesenchyme to form the multifaceted liver. Decades of research on liver development in mice and other vertebrates offer valuable lessons in how the multipotent endoderm is programmed to form a functional liver. Of equal importance are insights that have illuminated the mechanisms by which hepatic progenitors are activated in a damaged liver, how the adult liver regenerates, and, possibly, the basis for engineering liver cells in vitro for cell transplantation to sustain patients with liver failure. Moreover, processes that are key to liver development are often co-opted during pathogenesis. Therefore, reviewing hepatogenesis is informative for both basic and translational researchers. In this review, we bring to light the many advantages offered by the tropical freshwater vertebrate zebrafish (Danio rerio) in studying hepatogenesis. By comparing zebrafish and mice, we highlight how work in each system complements the other and emphasize novel paradigms that have been uncovered using zebrafish. Finally, we highlight exciting efforts using zebrafish to model hepatobiliary diseases. (HEPATOLOGY 2009.) [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]

Tailoring donor hepatectomy per segment 4 venous drainage in right lobe live donor liver transplantation

LIVER TRANSPLANTATION, Issue 6 2004
See Ching Chan
Including the middle hepatic vein (MHV) in the right lobe liver graft for adult-to-adult live donor liver transplantation provides more functional liver by securing adequate venous drainage. Donor outcome of this procedure in relation to different venous drainage patterns of segment 4 is unknown. Modification of graft harvesting technique by preserving segment 4b hepatic vein (V4b) in theory compensates for unfavorable venous drainage patterns. Consecutive 120 right lobe live donors were included. Computed tomography was studied in detail to assign each donor to one of the three types of the Nakamura classification of venous drainage pattern of segment 4. Type I drainage was mainly via the left hepatic vein (LHV), type II drainage was equally into the MHV and LHV, and type III drainage was predominantly into the MHV. Any distinct umbilical vein was also noted. In the early part of the series, the V4b draining into the MHV was divided to provide a long MHV stump in the graft. In the later part of the series, prominent V4b draining into the MHV was preserved in the donor as far as possible. Donor outcomes were measured by peak values of prothrombin time (PT), serum bilirubin and transaminases levels. There was no donor mortality. Type I donors (n=69) had the best outcome with peak PT of 17.9 sec (range 12.3,23.3 sec). Type II donors (n=44) had peak PT of 18.5 sec (range 15.4,24.4 sec). When V4b was preserved in type II donors (n=19), the peak PT (18.0 sec, range 15.4,20.7 sec) became significantly lower than that of type II donors who had V4b sacrificed (20.3 sec, range 16.2,24.4 sec) (P=0.001). A distinct umbilical vein (n=91, 75.8%) was insignificant for donor outcome measured by peak PT. Multivariate analysis identified that type II donors with V4b sacrificed (n=25), type III donors (n=7), and the first 50 cases had less favorable outcomes. In conclusion, unfavorable venous drainage patterns were one of the independent factors compromising postoperative donor liver function, but was circumvented by preservation of V4b. (Liver Transpl 2004;10:755,762.) [source]