scholarly journals Targeting Liver Sinusoidal Endothelial Cells: An Attractive Therapeutic Strategy to Control Inflammation in Nonalcoholic Fatty Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Xue-Kai Wang ◽  
Zong-Gen Peng
Keyword(s):  
Endothelial Cells ◽  
Liver Disease ◽  
Drug Development ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Liver Inflammation ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD), especially its advanced stage nonalcoholic steatohepatitis (NASH), has become a threatened public health problem worldwide. However, no specific drug has been approved for clinical use to treat patients with NASH, though there are many promising candidates against NAFLD in the drug development pipeline. Recently, accumulated evidence showed that liver sinusoidal endothelial cells (LSECs) play an essential role in the occurrence and development of liver inflammation in patients with NAFLD. LSECs, as highly specialized endothelial cells with unique structure and anatomical location, contribute to the maintenance of liver homeostasis and could be a promising therapeutic target to control liver inflammation of NAFLD. In this review, we outline the pathophysiological roles of LSECs related to inflammation of NAFLD, highlight the pro-inflammatory and anti-inflammatory effects of LSECs, and discuss the potential drug development strategies against NAFLD based on targeting to LSECs.

scholarly journals Serum microRNA-34a is potential biomarker for inflammation in nonalcoholic fatty liver disease

2017 ◽  
Vol 10 (2) ◽  
pp. 163-171 ◽  
Author(s):  
Puth Muangpaisarn ◽  
Kanisa Jampoka ◽  
Sunchai Payungporn ◽  
Naruemon Wisedopas ◽  
Chalermrat Bunchorntavakul ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Characteristic Curve ◽  
Control Group ◽  
Liver Inflammation ◽  
Apoptosis Pathway ◽  
Nonalcoholic Fatty Liver ◽  
Potential Biomarker

Abstract Background MicroRNA-34a (miR-34a) contributes to liver injury through an apoptosis pathway. Objective To determine the correlation between serum miR-34a and liver inflammation as assessed by nonalcoholic fatty liver disease (NAFLD) activity score (NAS). Method We included a cross-selectional study of 50 patients with NAFLD in this observational study and confirmed diagnosis by liver biopsy, with NAS grading. A control group comprised 23 healthy individuals without chronic liver disease. Serum miR-34a was assayed using a real-time quantitative PCR (Applied Biosystems). Result The mean age of NAFLD patients was 46.0 ± 13.7 years, and 52% were female. Metabolic syndrome was found in 76%. Liver histopathology showed that 54% of patients had NAS ≥4 and significant fibrosis (≥2) was found in 22%. Serum levels of miR-34a were significantly correlated with NAS (r = 0.39, P = 0.005), and the degree of steatosis (r = 0.28, P = 0.049), ballooning (r = 0.30, P = 0.034), and fibrosis (r = 0.39, P = 0.005). Serum miR-34a in patients with NAS ≥4 was significantly higher than in those with NAS <4 (P = 0.011) and controls (P < 0.001). There was no significant correlation between serum miR-34a and other variables. The area under receiver operating characteristic curve for serum miR-34a comparing patients with NAS ≥4 and with NAS <4 was 0.67 (95% CI 0.52, 0.82). Conclusion Serum level of miR-34a has a significant fair to good correlation with NAS and may serve as a biomarker of liver inflammation and fibrosis in patients with NAFLD.

scholarly journals Gut Microbiota as a Driver of Inflammation in Nonalcoholic Fatty Liver Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Stefano Bibbò ◽  
Gianluca Ianiro ◽  
Maria Pina Dore ◽  
Claudia Simonelli ◽  
Estelle E. Newton ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Liver Inflammation ◽  
Portal Circulation ◽  
Nonalcoholic Fatty Liver ◽  
Intestinal Dysbiosis ◽  
Insulin Dependent

The prevalence of nonalcoholic fatty liver disease and the consequent burden of metabolic syndrome have increased in recent years. Although the pathogenesis of nonalcoholic fatty liver disease is not completely understood, it is thought to be the hepatic manifestation of the dysregulation of insulin-dependent pathways leading to insulin resistance and adipose tissue accumulation in the liver. Recently, the gut-liver axis has been proposed as a key player in the pathogenesis of NAFLD, as the passage of bacteria-derived products into the portal circulation could lead to a trigger of innate immunity, which in turn leads to liver inflammation. Additionally, higher prevalence of intestinal dysbiosis, larger production of endogenous ethanol, and higher prevalence of increased intestinal permeability and bacterial translocation were found in patients with liver injury. In this review, we describe the role of intestinal dysbiosis in the activation of the inflammatory cascade in NAFLD.

scholarly journals New aspects of hepatic endothelial cells in physiology and nonalcoholic fatty liver disease

2020 ◽  
Vol 318 (6) ◽  
pp. C1200-C1213 ◽  
Author(s):  
Xinghui Sun ◽  
Edward N. Harris
Keyword(s):  
Endothelial Cells ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Paracrine Effects ◽  
Nonalcoholic Fatty Liver ◽  
Mesenchymal Transition ◽  
Endothelial To Mesenchymal Transition ◽  
Areas Of Interest

The liver is the central metabolic hub for carbohydrate, lipid, and protein metabolism. It is composed of four major types of cells, including hepatocytes, endothelial cells (ECs), Kupffer cells, and stellate cells. Hepatic ECs are highly heterogeneous in both mice and humans, representing the second largest population of cells in liver. The majority of them line hepatic sinusoids known as liver sinusoidal ECs (LSECs). The structure and biology of LSECs and their roles in physiology and liver disease were reviewed recently. Here, we do not give a comprehensive review of LSEC structure, function, or pathophysiology. Instead, we focus on the recent progress in LSEC research and other hepatic ECs in physiology and nonalcoholic fatty liver disease and other hepatic fibrosis-related conditions. We discuss several current areas of interest, including capillarization, scavenger function, autophagy, cellular senescence, paracrine effects, and mechanotransduction. In addition, we summarize the strengths and weaknesses of evidence for the potential role of endothelial-to-mesenchymal transition in liver fibrosis.

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