scholarly journals In vivo consequences of liver-specific interleukin-22 expression in mice: Implications for human liver disease progression

Hepatology ◽  
2011 ◽  
Vol 54 (1) ◽  
pp. 252-261 ◽  
Author(s):  
Ogyi Park ◽  
Hua Wang ◽  
Honglei Weng ◽  
Lionel Feigenbaum ◽  
Hai Li ◽  
...  
Keyword(s):  
Liver Disease ◽  
Disease Progression ◽  
Human Liver ◽  
Interleukin 22 ◽  
Liver Disease Progression ◽  
Human Liver Disease

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.

scholarly journals Dynamin-related protein 1 deficiency impairs mitophagy and accelerates lipopolysaccharide-induced inflammation in mice

2020 ◽  
Author(s):  
Lixiang Wang ◽  
Xin Li ◽  
Yuki Hanada ◽  
Nao Hasuzawa ◽  
Masatoshi Nomura ◽  
...  
Keyword(s):  
Liver Disease ◽  
Disease Progression ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Mitochondrial Fusion ◽  
Inflammasome Activation ◽  
Disease Development ◽  
Related Protein ◽  
Liver Disease Progression

Abstract Mitochondrial fusion and fission, which are strongly related to normal mitochondrial function, are referred to as mitochondrial dynamics. Mitochondrial fusion defects in the liver cause a non-alcoholic steatohepatitis-like phenotype and liver cancer. However, whether mitochondrial fission defect directly impair liver function and stimulate liver disease progression, too, is unclear. Dynamin-related protein 1 (DRP1) is a key factor controlling mitochondrial fission. We hypothesized that DRP1 defects are a causal factor directly involved in liver disease development and stimulate liver disease progression. We administered lipopolysaccharide (LPS) to liver-specific Drp1-knockout (Drp1LiKO) mice. We observed an enhanced inflammatory response accompanied by mitophagy impairment. Drp1 defects directly promoted hepatocyte apoptosis and subsequently induced infiltration of inflammatory macrophages enhanced inflammasome activation in the liver and increased pro-inflammatory cytokine expression in the liver and serum. Drp1 deletion increased the expression of numerous genes involved in the immune response and DNA damage in Drp1LiKO mouse primary hepatocytes. This is a novel mechanism of liver disease development in which Drp1 defect-induced mitochondrial dynamics dysfunction directly regulates the fate and function of hepatocytes and enhances LPS-induced acute liver injure in vivo.

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

1894-P: HIF-2α Induced by Hypoxia Exacerbates Nonalcoholic Fatty Liver Disease Progression via Suppressing PPARα

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1894-P
Author(s):  
JIANDI CHEN ◽  
JIANXU CHEN ◽  
HUIRONG FU ◽  
YUN LI ◽  
SHUNKUI LUO ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Disease Progression ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Liver Disease Progression

scholarly journals Genetic variants of programmed cell death 1 are associated with HBV infection and liver disease progression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nghiem Xuan Hoan ◽  
Pham Thi Minh Huyen ◽  
Mai Thanh Binh ◽  
Ngo Tat Trung ◽  
Dao Phuong Giang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Liver Disease ◽  
Programmed Cell Death ◽  
Disease Progression ◽  
Infection Risk ◽  
Hbv Infection ◽  
Liver Disease Progression ◽  
Increased Risk ◽  
Programmed Cell Death 1

AbstractThe inhibitory effects of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) modulates T-cell depletion. T-cell depletion is one of the key mechanisms of hepatitis B virus (HBV) persistence, in particular liver disease progression and the development of hepatocellular carcinoma (HCC). This case–control study aimed to understand the significance of PD-1 polymorphisms (PD-1.5 and PD-1.9) association with HBV infection risk and HBV-induced liver disease progression. Genotyping of PD-1.5 and PD-1.9 variants was performed by direct Sanger sequencing in 682 HBV-infected patients including chronic hepatitis (CHB, n = 193), liver cirrhosis (LC, n = 183), hepatocellular carcinoma (HCC, n = 306) and 283 healthy controls (HC). To analyze the association of PD-1 variants with liver disease progression, a binary logistic regression, adjusted for age and gender, was performed using different genetic models. The PD-1.9 T allele and PD-1.9 TT genotype are significantly associated with increased risk of LC, HCC, and LC + HCC. The frequencies of PD-1.5 TT genotype and PD-1.5 T allele are significantly higher in HCC compared to LC patients. The haplotype CT (PD-1.5 C and PD-1.9 T) was significantly associated with increased risk of LC, HCC, and LC + HCC. In addition, the TC (PD-1.5 T and PD-1.9 C) haplotype was associated with the risk of HCC compared to non-HCC. The PD-1.5 CC, PD-1.9 TT, genotype, and the CC (PD-1.5 C and PD-1.9) haplotype are associated with unfavorable laboratory parameters in chronic hepatitis B patients. PD-1.5 and PD1.9 are useful prognostic predictors for HBV infection risk and liver disease progression.

Serum Xanthine Oxidase in Human Liver Disease

2001 ◽  
Vol 96 (4) ◽  
pp. 1194-1199 ◽  
Author(s):  
Maria Giulia Battelli ◽  
Silvia Musiani ◽  
Marco Valgimigli ◽  
Laura Gramantieri ◽  
Federica Tomassoni ◽  
...  
Keyword(s):  
Liver Disease ◽  
Xanthine Oxidase ◽  
Human Liver ◽  
Human Liver Disease

Impact of genotype 3 on clinical outcome in patients with hepatitis C: both diabetes meliitus and liver disease progression

2017 ◽  
Vol 66 (1) ◽  
pp. S711-S712
Author(s):  
W. Zanjir ◽  
R. Maan ◽  
B. Hansen ◽  
O. Cerocchi ◽  
H. Janssen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Hepatitis C ◽  
Clinical Outcome ◽  
Disease Progression ◽  
Genotype 3 ◽  
Liver Disease Progression

Plasma lysozyme level and reticuloendothelial system function in human liver disease

1981 ◽  
Vol 113 (2) ◽  
pp. 193-199 ◽  
Author(s):  
Adrie CM. van Vliet ◽  
W.H. Bakker ◽  
J. Lindemans ◽  
J.H.P. Wilson ◽  
R.A.A. van Zanten
Keyword(s):  
Liver Disease ◽  
Human Liver ◽  
Reticuloendothelial System ◽  
System Function ◽  
Human Liver Disease

scholarly journals Dynamin-related protein 1 deficiency accelerates lipopolysaccharide-induced acute liver injury and inflammation in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Lixiang Wang ◽  
Xin Li ◽  
Yuki Hanada ◽  
Nao Hasuzawa ◽  
Yoshinori Moriyama ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Er Stress ◽  
Disease Progression ◽  
Acute Liver Injury ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Mitochondrial Fusion ◽  
Related Protein ◽  
Liver Disease Progression

AbstractMitochondrial fusion and fission, which are strongly related to normal mitochondrial function, are referred to as mitochondrial dynamics. Mitochondrial fusion defects in the liver cause a non-alcoholic steatohepatitis-like phenotype and liver cancer. However, whether mitochondrial fission defect directly impair liver function and stimulate liver disease progression, too, is unclear. Dynamin-related protein 1 (DRP1) is a key factor controlling mitochondrial fission. We hypothesized that DRP1 defects are a causal factor directly involved in liver disease development and stimulate liver disease progression. Drp1 defects directly promoted endoplasmic reticulum (ER) stress, hepatocyte death, and subsequently induced infiltration of inflammatory macrophages. Drp1 deletion increased the expression of numerous genes involved in the immune response and DNA damage in Drp1LiKO mouse primary hepatocytes. We administered lipopolysaccharide (LPS) to liver-specific Drp1-knockout (Drp1LiKO) mice and observed an increased inflammatory cytokine expression in the liver and serum caused by exaggerated ER stress and enhanced inflammasome activation. This study indicates that Drp1 defect-induced mitochondrial dynamics dysfunction directly regulates the fate and function of hepatocytes and enhances LPS-induced acute liver injury in vivo.

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