scholarly journals Hepatocyte size fractionation allows dissection of human liver zonation

2021 ◽  
Author(s):  
Magnus Ölander ◽  
Christine Wegler ◽  
Inken Flörkemeier ◽  
Andrea Treyer ◽  
Niklas Handin ◽  
...  
Keyword(s):  
Human Liver ◽  
Size Fractionation ◽  
Liver Zonation

scholarly journals Pre-clinical and clinical investigations of metabolic zonation in liver diseases: The potential of microphysiology systems

2017 ◽  
Vol 242 (16) ◽  
pp. 1605-1616 ◽  
Author(s):  
Alejandro Soto-Gutierrez ◽  
Albert Gough ◽  
Lawrence A Vernetti ◽  
DL Taylor ◽  
Satdarshan P Monga
Keyword(s):  
Gene Expression ◽  
Liver Disease ◽  
Disease Progression ◽  
Liver Diseases ◽  
Human Liver ◽  
Liver Zonation ◽  
Metabolic Zonation ◽  
Liver Disease Progression ◽  
And Function

The establishment of metabolic zonation within a hepatic lobule ascribes specific functions to hepatocytes based on unique, location-dependent gene expression patterns. Recently, there have been significant developments in the field of metabolic liver zonation. A little over a decade ago, the role of β-catenin signaling was identified as a key regulator of gene expression and function in pericentral hepatocytes. Since then, additional molecules have been identified that regulate the pattern of Wnt/β-catenin signaling within a lobule and determine gene expression and function in other hepatic zones. Currently, the molecular basis of metabolic zonation in the liver appears to be a ‘push and pull’ between signaling pathways. Such compartmentalization not only provides an efficient assembly line for hepatocyte functions but also can account for restricting the initial hepatic damage and pathology from some hepatotoxic drugs to specific zones, possibly enabling effective regeneration and restitution responses from unaffected cells. Careful analysis and experimentation have also revealed that many pathological conditions in the liver lobule are spatially heterogeneous. We will review current research efforts that have focused on examination of the role and regulation of such mechanisms of hepatocyte adaptation and repair. We will discuss how the pathological organ-specific microenvironment affects cell signaling and metabolic liver zonation, especially in steatosis, viral hepatitis, and hepatocellular carcinoma. We will discuss how the use of new human microphysiological platforms will lead to a better understanding of liver disease progression, diagnosis, and therapies. In conclusion, we aim to provide insights into the role and regulation of metabolic zonation and function using traditional and innovative approaches. Impact statement Liver zonation of oxygen tension along the liver sinusoids has been identified as a critical liver microenvironment that impacts specific liver functions such as intermediary metabolism of amino acids, lipids, and carbohydrates, detoxification of xenobiotics and as sites for initiation of liver diseases. To date, most information on the role of zonation in liver disease including, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC) have been obtained from animal models. It is now possible to complement animal studies with human liver, microphysiology systems (MPS) containing induced pluripotent stem cells engineered to create disease models where it is also possible to control the in vitro liver oxygen microenvironment to define the role of zonation on the mechanism(s) of disease progression. The field now has the tools to investigate human liver disease progression, diagnosis, and therapeutic development.

Deactivation of anti-cancer drug letrozole to a carbinol metabolite by polymorphic cytochrome P450 2A6 in human liver microsomes

Xenobiotica ◽  
2009 ◽  
Vol 00 (00) ◽  
pp. 090901052053001-8
Author(s):  
K. Murai ◽  
H. Yamazaki ◽  
K. Nakagawa ◽  
R. Kawai ◽  
T. Kamataki
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Cytochrome P450 2A6

Author response for "Human liver‐derived MAIT cells differ from blood MAIT cells in their metabolism and response to TCR‐independent activation"

2020 ◽  
Author(s):  
Rajesh Lamichhane ◽  
Fran Munro ◽  
Thomas W. R. Harrop ◽  
Sara M. Harpe ◽  
Peter K. Dearden ◽  
...  
Keyword(s):  
Human Liver ◽  
Author Response ◽  
Mait Cells

Selegiline Metabolism and Cytochrome P450 Enzymes:In vitro Study in Human Liver Microsomes*

2000 ◽  
Vol 86 (5) ◽  
pp. 215-221 ◽  
Author(s):  
Paivi Taavitsainen ◽  
Markku Anttila ◽  
Leena Nyman ◽  
Hari Karnani ◽  
Jarmo S. Salonen ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Vitro Study

Human Liver Cocaine Carboxylesterases

1997 ◽  
Author(s):  
William F. Bosron ◽  
Robert A. Dean ◽  
Monica R. Brzezinski ◽  
Evgenia V. Pindel
Keyword(s):  
Human Liver

Human liver cell cultivation for long-term in vitro toxicity studies in a miniaturized multi-compartment 3D bioreactor system

2011 ◽  
Vol 49 (01) ◽  
Author(s):  
SA Hoffmann ◽  
M Lübberstedt ◽  
U Müller-Vieira ◽  
D Knobeloch ◽  
A Nüssler ◽  
...  
Keyword(s):  
Liver Cell ◽  
Human Liver ◽  
In Vitro Toxicity ◽  
Cell Cultivation ◽  
Toxicity Studies ◽  
Human Liver Cell ◽  
Bioreactor System

EpCam-specific Gold Nanoparticles for Detection, Live-imaging and Rapid Enrichment of Adult Human Liver Progenitor Cells

2013 ◽  
Vol 51 (01) ◽  
Author(s):  
N Fekete-Drimusz ◽  
J de la Roche ◽  
F Vondran ◽  
CL Sajti ◽  
MP Manns ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Progenitor Cells ◽  
Human Liver ◽  
Live Imaging ◽  
Adult Human

Keratins 8/18 represent type II acute-phase proteins which are differentially regulated in human liver disease

2013 ◽  
Vol 51 (01) ◽  
Author(s):  
N Güldiken ◽  
V Usachov ◽  
K Levada ◽  
M Ziol ◽  
P Nahon ◽  
...  
Keyword(s):  
Liver Disease ◽  
Acute Phase ◽  
Human Liver ◽  
Acute Phase Proteins ◽  
Type Ii ◽  
Human Liver Disease
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