scholarly journals Toll-Like Receptor 3 in Liver Diseases

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Shi Yin ◽  
Bin Gao
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Immune Cells ◽  
Liver Diseases ◽  
Human Liver ◽  
Toll Like Receptor ◽  
Double Stranded Rna ◽  
Nonparenchymal Cells

Toll-like receptor 3 (TLR3) is a member of the TLR family that can recognize double-stranded RNA (dsRNA), playing an important role in antiviral immunity. Recent studies have shown that TLR3 is also expressed on parenchymal and nonparenchymal cells in the liver as well as on several types of immune cells. In this review, we summarize the role of TLR3 in liver injury, inflammation, regeneration, and liver fibrosis, and discuss the implication of TLR3 in the pathogenesis of human liver diseases including viral hepatitis and autoimmune liver disease.

scholarly journals The Role of the Gut Microbiome in Liver Cirrhosis Treatment

2020 ◽  
Vol 22 (1) ◽  
pp. 199
Author(s):  
Na Young Lee ◽  
Ki Tae Suk
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Chronic Liver ◽  
Chronic Liver Diseases

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis.

scholarly journals Neutrophils in liver diseases: pathogenesis and therapeutic targets

2020 ◽  
Vol 18 (1) ◽  
pp. 38-44 ◽  
Author(s):  
Kai Liu ◽  
Fu-Sheng Wang ◽  
Ruonan Xu
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Cancer ◽  
Immune Regulation ◽  
Liver Diseases ◽  
Immune Modulation ◽  
Functional Plasticity ◽  
Homogeneous Population ◽  
Patients With Cancer

AbstractPreviously, it was assumed that peripheral neutrophils are a homogeneous population that displays antimicrobial functions. However, recent data have revealed that neutrophils are heterogeneous and are additionally involved in tissue damage and immune regulation. The phenotypic and functional plasticity of neutrophils has been identified in patients with cancer, inflammatory disorders, infections, and other diseases. Currently, neutrophils, with their autocrine, paracrine, and immune modulation functions, have been shown to be involved in liver diseases, including viral hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, liver fibrosis, cirrhosis, liver failure, and liver cancer. Accordingly, this review summarizes the role of neutrophils in liver diseases.

MicroRNAs as regulators, biomarkers and therapeutic targets in liver diseases

Gut ◽  
2020 ◽  
pp. gutjnl-2020-322526
Author(s):  
Xiaolin Wang ◽  
Yong He ◽  
Bryan Mackowiak ◽  
Bin Gao
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Liver Diseases ◽  
Target Genes ◽  
Therapeutic Targets ◽  
Drug Induced ◽  
Alcoholic Fatty Liver ◽  
Altered Expression ◽  
Mrna Targets

MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene expression by binding to specific mRNA targets and promoting their degradation and/or translational inhibition. miRNAs regulate both physiological and pathological liver functions. Altered expression of miRNAs is associated with liver metabolism dysregulation, liver injury, liver fibrosis and tumour development, making miRNAs attractive therapeutic strategies for the diagnosis and treatment of liver diseases. Here, we review recent advances regarding the regulation and function of miRNAs in liver diseases with a major focus on miRNAs that are specifically expressed or enriched in hepatocytes (miR-122, miR-194/192), neutrophils (miR-223), hepatic stellate cells (miR-29), immune cells (miR-155) and in circulation (miR-21). The functions and target genes of these miRNAs are emphasised in alcohol-associated liver disease, non-alcoholic fatty liver disease, drug-induced liver injury, viral hepatitis and hepatocellular carcinoma, as well liver fibrosis and liver failure. We touch on the roles of miRNAs in intercellular communication between hepatocytes and other types of cells via extracellular vesicles in the pathogenesis of liver diseases. We provide perspective on the application of miRNAs as biomarkers for early diagnosis, prognosis and assessment of liver diseases and discuss the challenges in miRNA-based therapy for liver diseases. Further investigation of miRNAs in the liver will help us better understand the pathogeneses of liver diseases and may identify biomarkers and therapeutic targets for liver diseases in the future.

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.

miR-223 represents a biomarker in acute and chronic liver injury

2017 ◽  
Vol 131 (15) ◽  
pp. 1971-1987 ◽  
Author(s):  
Florian Schueller ◽  
Sanchari Roy ◽  
Sven Heiko Loosen ◽  
Jan Alder ◽  
Christiane Koppe ◽  
...  
Keyword(s):  
Cell Death ◽  
Liver Cirrhosis ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Liver Diseases ◽  
Acute Liver Injury ◽  
Chronic Liver ◽  
Published Data ◽  
Duct Ligation

Background: Dysregulation of miRNAs has been described in tissue and serum from patients with acute and chronic liver diseases. However, only little information on the role of miR-223 in the pathophysiology of acute liver failure (ALF) and liver cirrhosis is available. Methods: We analysed cell and tissue specific expression levels as well as serum concentrations of miR-223 in mouse models of acute (hepatic ischaemia and reperfusion, single CCl4 injection) and chronic (repetitive CCl4 injection, bile duct ligation (BDL)) liver diseases. Results were validated in patients and correlated with clinical data. The specific hepatic role of miR-223 was analysed by using miR-223−/− mice in these models. Results: miR-223 expression was significantly dysregulated in livers from mice after induction of acute liver injury and liver fibrosis as well as in liver samples from patients with ALF or liver cirrhosis. In acute and chronic models, hepatic miR-223 up-regulation was restricted to hepatocytes and correlated with degree of liver injury and hepatic cell death. Moreover, elevated miR-223 expression was reflected by significantly higher serum levels of miR-223 during acute liver injury. However, functional in vitro and in vivo experiments revealed no differences in the degree of liver cell death and liver fibrosis as miR-223−/− mice behaved identical with wild-type (wt) mice in all tested models. Conclusion: miR-223 represents a promising diagnostic marker in a panel of serum markers of liver injury. Together with previously published data, our results highlight that the role of miR-223 in the pathophysiology of the liver is complex and needs further analysis.

scholarly journals The Role of the Gut Microbiome in Liver Fibrosis

2020 ◽  
Author(s):  
Na Young Lee ◽  
Ki Tae Suk
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Chronic Liver ◽  
Chronic Liver Diseases

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, genetic conditions such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis, and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease from other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver cirrhosis.

Role of TGR5 (GPBAR1) in Liver Disease

2018 ◽  
Vol 38 (04) ◽  
pp. 333-339 ◽  
Author(s):  
Dieter Häussinger ◽  
Verena Keitel
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Primary Biliary Cholangitis ◽  
Extrahepatic Cholangiocarcinoma ◽  
Nonparenchymal Cells ◽  
Polycystic Liver ◽  
Liver Injuries ◽  
G Protein Coupled ◽  
Secondary Bile Acids

AbstractTGR5 (GPBAR1) is a G protein–coupled receptor activated by primary and secondary bile acids, which is expressed in different nonparenchymal cells of the liver, such as sinusoidal endothelial cells, Kupffer cells, cholangiocytes as well as activated hepatic stellate cells. In liver, TGR5 modulates microcirculation, inflammation, regeneration, biliary secretion and proliferation as well as gallbladder filling. Absence of TGR5 renders mice more susceptible toward infectious, inflammatory, metabolic as well as cholestatic liver injuries. It is unknown whether TGR5 plays a role in the pathogenesis of human nonalcoholic steatohepatitis and cholestatic liver diseases such as primary sclerosing cholangitis and primary biliary cholangitis. However, overexpression of TGR5 has been detected in human intra- and extrahepatic cholangiocarcinoma as well as in cystic cholangiocytes, where the receptor promotes cell proliferation, anti-apoptosis as well as cyst growth. While TGR5 agonists may improve various aspects of metabolic, inflammatory, and cholestatic liver diseases, TGR5 inhibitors may attenuate disease progression in polycystic liver disease and cholangiocarcinoma.

A polysaccharide of PFP-1 from Pleurotus geesteranus attenuates alcoholic liver diseases via Nrf2 and NF-κB signaling pathways

2021 ◽  
Author(s):  
Xinling Song ◽  
Wenxue Sun ◽  
Wenxin Cai ◽  
Le Jia ◽  
Jianjun Zhang
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Liver Injury ◽  
Signaling Pathways ◽  
Alcoholic Liver Disease ◽  
Fruiting Body ◽  
Liver Diseases ◽  
Alcoholic Liver Diseases

A polysaccharide named as PFP-1 was isolated from Pleurotus geesteranus fruiting body, and the potential investigations on ameliorating oxidative stress and liver injury against alcoholic liver disease (ALD) were processed...

scholarly journals Possible unrecognised liver injury is associated with mortality in critically ill COVID-19 patients

2021 ◽  
Vol 14 ◽  
pp. 175628482110234
Author(s):  
Mario Romero-Cristóbal ◽  
Ana Clemente-Sánchez ◽  
Patricia Piñeiro ◽  
Jamil Cedeño ◽  
Laura Rayón ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Chronic Liver Disease ◽  
Critically Ill ◽  
Cox Regression ◽  
Chronic Liver ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
The Impact

Background: Coronavirus disease (COVID-19) with acute respiratory distress syndrome is a life-threatening condition. A previous diagnosis of chronic liver disease is associated with poorer outcomes. Nevertheless, the impact of silent liver injury has not been investigated. We aimed to explore the association of pre-admission liver fibrosis indices with the prognosis of critically ill COVID-19 patients. Methods: The work presented was an observational study in 214 patients with COVID-19 consecutively admitted to the intensive care unit (ICU). Pre-admission liver fibrosis indices were calculated. In-hospital mortality and predictive factors were explored with Kaplan–Meier and Cox regression analysis. Results: The mean age was 59.58 (13.79) years; 16 patients (7.48%) had previously recognised chronic liver disease. Up to 78.84% of patients according to Forns, and 45.76% according to FIB-4, had more than minimal fibrosis. Fibrosis indices were higher in non-survivors [Forns: 6.04 (1.42) versus 4.99 (1.58), p < 0.001; FIB-4: 1.77 (1.17) versus 1.41 (0.91), p = 0.020)], but no differences were found in liver biochemistry parameters. Patients with any degree of fibrosis either by Forns or FIB-4 had a higher mortality, which increased according to the severity of fibrosis ( p < 0.05 for both indexes). Both Forns [HR 1.41 (1.11–1.81); p = 0.006] and FIB-4 [HR 1.31 (0.99–1.72); p = 0.051] were independently related to survival after adjusting for the Charlson comorbidity index, APACHE II, and ferritin. Conclusion: Unrecognised liver fibrosis, assessed by serological tests prior to admission, is independently associated with a higher risk of death in patients with severe COVID-19 admitted to the ICU.

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