scholarly journals Liver injury changed the biological characters of serum small extracellular vesicles and reprogramed hepatic macrophages in mice

2021 ◽  
Author(s):  
Xiufang Lv ◽  
Jing Li ◽  
Li He ◽  
Li Cheng ◽  
Min Zhao ◽  
...  
Keyword(s):  
Liver Injury ◽  
Extracellular Vesicles ◽  
Liver Diseases ◽  
Human Liver ◽  
Mouse Liver ◽  
Liver Steatosis ◽  
Biological Significance ◽  
Circulating Mirnas ◽  
Hepatic Macrophages ◽  
Liver Macrophage

Abstract Background Serum small extracellular vesicles (sEVs) and their small RNA (sRNA) cargoes could be promising biomarkers for the diagnosis of liver injury. However, the dynamic changes of serum sEVs and their sRNA components during liver injury and the biological functions of these liver-injury-serum sEVs have not been well characterized. Methods To identify serum sEV biomarkers for liver injury, we established a carbon tetrachloride-induced mouse liver injury model to simulate acute liver injury (ALI), chronic liver injury (CLI) and recovery. Serum sEVs were obtained and characterized. Serum sEV sRNAs were profiled. Differentially expressed microRNAs (miRNA) were compared to mouse liver enriched miRNAs and previously reported circulating miRNAs that related to human liver diseases. The biological significance was evaluated by Ingenuity Pathway Analysis of altered sEV miRNAs, and conditional culture of ALI serum sEVs with primary hepatic macrophages. Results We found that both ALI and CLI changed the concentration and morphology of serum sEVs. The proportion of serum sEV miRNA increased upon liver injury, with the liver as the primary contributor. The altered serum sEV miRNAs based on mice's study were consistent with those human liver diseases-related circulating miRNAs. Serum sEV miRNA signatures for ALI and CLI, and a panel of miRNAs as common marker for liver injury, were established. The differential serum sEV miRNAs in ALI mainly contributed to liver steatosis and inflammation, while those in CLI primarily contributed to hepatocellular carcinoma and hyperplasia. ALI serum sEVs decreased both CD86 and CD206 expression in monocyte-derived macrophages, but increased CD206 expression in resident macrophages. Conclusion Serum sEVs in the different stages of liver injury carried different sRNA messages and contributed to diverse pathological processes. ALI serum sEVs might alleviate liver damage by depolarizing monocyte-derived macrophages and educating resident liver macrophage to M2 like cells.

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 Caveolin-1 Deficiency Protects Mice Against Carbon Tetrachloride-Induced Acute Liver Injury Through Regulating Polarization of Hepatic Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Ziheng Yang ◽  
Jie Zhang ◽  
Yan Wang ◽  
Jing Lu ◽  
Quan Sun
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Liver Diseases ◽  
Acute Liver Injury ◽  
Mrna Levels ◽  
Alcoholic Fatty Liver ◽  
Caveolin 1 ◽  
Hepatic Macrophages ◽  
M1 Phenotype

Polarization of hepatic macrophages plays a crucial role in the injury and repair processes of acute and chronic liver diseases. However, the underlying molecular mechanisms remain elusive. Caveolin-1 (Cav1) is the structural protein of caveolae, the invaginations of the plasma membrane. It has distinct functions in regulating hepatitis, cirrhosis, and hepatocarcinogenesis. Given the increasing number of cases of liver cancer, nonalcoholic steatohepatitis, and non-alcoholic fatty liver disease worldwide, investigations on the role of Cav1 in liver diseases are warranted. In this study, we aimed to investigate the role of Cav1 in the pathogenesis of acute liver injury. Wild-type (WT) and Cav1 knockout (KO) mice (Cav1tm1Mls) were injected with carbon tetrachloride (CCl4). Cav1 KO mice showed significantly reduced degeneration, necrosis, and apoptosis of hepatocytes and decreased level of alanine transaminase (ALT) compared to WT mice. Moreover, Cav1 was required for the recruitment of hepatic macrophages. The analysis of the mRNA levels of CD86, tumor necrosis factor (TNF), and interleukin (IL)-6, as well as the protein expression of inducible nitric oxide synthase (iNOS), indicated that Cav1 deficiency inhibited the polarization of hepatic macrophages towards the M1 phenotype in the injured liver. Consistent with in vivo results, the expressions of CD86, TNF, IL-6, and iNOS were significantly downregulated in Cav1 KO macrophages. Also, fluorescence-activated cell sorting (FACS) analysis showed that the proportion of M1 macrophages was significantly decreased in the liver tissues obtained from Cav1 KO mice following CCl4 treatment. In summary, our results showed that Cav1 deficiency protected mice against CCl4-induced acute liver injury by regulating polarization of hepatic macrophages. We provided direct genetic evidence that Cav1 expressed in hepatic macrophages contributed to the pathogenesis of acute liver injury by regulating the polarization of hepatic macrophages towards the M1 phenotype. These findings suggest that Cav1 expressed in macrophages may represent a potential therapeutic target for acute liver injury.

scholarly journals ARRB1 suppresses the activation of hepatic macrophages via modulating endoplasmic reticulum stress in lipopolysaccharide-induced acute liver injury

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yiming Lei ◽  
Sizhe Wan ◽  
Huiling Liu ◽  
Haoxiong Zhou ◽  
Lingjun Chen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Liver Injury ◽  
Er Stress ◽  
Cell Lines ◽  
Macrophage Activation ◽  
Acute Liver Injury ◽  
Vital Event ◽  
Hepatic Macrophages ◽  
Liver Macrophage ◽  
Hepatic Macrophage

AbstractAcute liver injury (ALI) caused by multiple inflammatory responses is a monocyte-/macrophage-mediated liver injury that is associated with high morbidity and mortality. Liver macrophage activation is a vital event that triggers ALI. However, the mechanism of liver macrophage activation has not been fully elucidated. This study examined the role of β-arrestin1 (ARRB1) in wild-type (WT) and ARRB1-knockout (ARRB1-KO) mouse models of ALI induced by lipopolysaccharide (LPS), and ARRB1-KO mice exhibited more severe inflammatory injury and liver macrophage activation compared to WT mice. We found that LPS treatment reduced the expression level of ARRB1 in Raw264.7 and THP-1 cell lines, and mouse primary hepatic macrophages. Overexpression of ARRB1 in Raw264.7 and THP-1 cell lines significantly attenuated LPS-induced liver macrophage activation, such as transformation in cell morphology and enhanced expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), while downregulation of ARRB1 by small interfering RNA and ARRB1 deficiency in primary hepatic macrophages both aggravated macrophage activation. Moreover, overexpression of ARRB1 suppressed LPS-induced endoplasmic reticulum (ER) stress in liver macrophages, and inhibition of ER stress impeded excessive hepatic macrophage activation induced by downregulation of ARRB1. Our data demonstrate that ARRB1 relieves LPS-induced ALI through the ER stress pathway to regulate hepatic macrophage activation and that ARRB1 may be a potential therapeutic target for ALI.

scholarly journals Liver injury changes the biological characters of serum small extracellular vesicles and reprograms hepatic macrophages in mice

2021 ◽  
Vol 27 (43) ◽  
pp. 7509-7529
Author(s):  
Xiu-Fang Lv ◽  
An-Qi Zhang ◽  
Wei-Qi Liu ◽  
Min Zhao ◽  
Jing Li ◽  
...  
Keyword(s):  
Liver Injury ◽  
Extracellular Vesicles ◽  
Hepatic Macrophages ◽  
Biological Characters

Lipocalin-2 (LCN2) in experimental liver injury and human liver diseases

2011 ◽  
Vol 49 (01) ◽  
Author(s):  
E Borkham-Kamphorst ◽  
HW Zimmermann ◽  
KR Karlmark ◽  
E Van de Leur ◽  
J Bauer ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Diseases ◽  
Human Liver ◽  
Lipocalin 2 ◽  
Experimental Liver

scholarly journals The Anti-Microbial Peptide LL-37/CRAMP Is Elevated in Patients with Liver Diseases and Acts as a Protective Factor during Mouse Liver Injury

Digestion ◽  
2015 ◽  
Vol 91 (4) ◽  
pp. 307-317 ◽  
Author(s):  
Svenja Wertenbruch ◽  
Hannah Drescher ◽  
Vera Grossarth ◽  
Daniela Kroy ◽  
Arne Giebeler ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Diseases ◽  
Mouse Liver ◽  
Protective Factor

Comparison of Thy–1 expression in human liver cirrhosis and different models of rat liver injury

2006 ◽  
Vol 44 (01) ◽  
Author(s):  
T Mansuroglu ◽  
J Dudas ◽  
B Saile ◽  
D Batusic ◽  
G Ramadori
Keyword(s):  
Liver Cirrhosis ◽  
Liver Injury ◽  
Rat Liver ◽  
Human Liver ◽  
Human Liver Cirrhosis

Effects of Extracellular Vesicles Derived from Mesenchymal Stem/Stromal Cells on Liver Diseases

2019 ◽  
Vol 14 (5) ◽  
pp. 442-452 ◽  
Author(s):  
Wenjie Zheng ◽  
Yumin Yang ◽  
Russel Clive Sequeira ◽  
Colin E. Bishop ◽  
Anthony Atala ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Liver Diseases ◽  
Therapeutic Potential ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Chronic Liver Injury ◽  
Mediated Effects ◽  
Therapeutic Benefits

Therapeutic effects of Mesenchymal Stem/Stromal Cells (MSCs) transplantation have been observed in various disease models. However, it is thought that MSCs-mediated effects largely depend on the paracrine manner of secreting cytokines, growth factors, and Extracellular Vesicles (EVs). Similarly, MSCs-derived EVs also showed therapeutic benefits in various liver diseases through alleviating fibrosis, improving regeneration of hepatocytes, and regulating immune activity. This review provides an overview of the MSCs, their EVs, and their therapeutic potential in treating various liver diseases including liver fibrosis, acute and chronic liver injury, and Hepatocellular Carcinoma (HCC). More specifically, the mechanisms by which MSC-EVs induce therapeutic benefits in liver diseases will be covered. In addition, comparisons between MSCs and their EVs were also evaluated as regenerative medicine against liver diseases. While the mechanisms of action and clinical efficacy must continue to be evaluated and verified, MSCs-derived EVs currently show tremendous potential and promise as a regenerative medicine treatment for liver disease in the future.

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