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

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 Liver Injury and the Macrophage Issue: Molecular and Mechanistic Facts and Their Clinical Relevance

2021 ◽  
Vol 22 (14) ◽  
pp. 7249
Author(s):  
Siyer Roohani ◽  
Frank Tacke
Keyword(s):  
Bone Marrow ◽  
Liver Injury ◽  
Current Knowledge ◽  
Hepatocellular Cancer ◽  
Complete Recovery ◽  
Hepatic Macrophages ◽  
Liver Injuries ◽  
Microbial Products ◽  
Injured Liver

The liver is an essential immunological organ due to its gatekeeper position to bypassing antigens from the intestinal blood flow and microbial products from the intestinal commensals. The tissue-resident liver macrophages, termed Kupffer cells, represent key phagocytes that closely interact with local parenchymal, interstitial and other immunological cells in the liver to maintain homeostasis and tolerance against harmless antigens. Upon liver injury, the pool of hepatic macrophages expands dramatically by infiltrating bone marrow-/monocyte-derived macrophages. The interplay of the injured microenvironment and altered macrophage pool skews the subsequent course of liver injuries. It may range from complete recovery to chronic inflammation, fibrosis, cirrhosis and eventually hepatocellular cancer. This review summarizes current knowledge on the classification and role of hepatic macrophages in the healthy and injured liver.

Extracellular vesicles derived from human embryonic stem cell‐MSCs ameliorate cirrhosis in thioacetamide‐induced chronic liver injury

2018 ◽  
Vol 233 (12) ◽  
pp. 9330-9344 ◽  
Author(s):  
Soura Mardpour ◽  
Seyedeh‐Nafiseh Hassani ◽  
Saeid Mardpour ◽  
Forough Sayahpour ◽  
Massoud Vosough ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Injury ◽  
Embryonic Stem Cell ◽  
Extracellular Vesicles ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Chronic Liver ◽  
Chronic Liver Injury

Contribution of complement-stimulated hepatic macrophages and neutrophils to endotoxin-induced liver injury in rats

Hepatology ◽  
1994 ◽  
Vol 19 (4) ◽  
pp. 973-979 ◽  
Author(s):  
Hartmut Jaeschke ◽  
Anwar Farhood ◽  
C. Wayne Smith
Keyword(s):  
Liver Injury ◽  
Hepatic Macrophages

scholarly journals IL-1 receptor like 1 protects against alcoholic liver injury by limiting NF-κB activation in hepatic macrophages

2018 ◽  
Vol 68 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Meng Wang ◽  
Guannan Shen ◽  
Liangguo Xu ◽  
Xiaodong Liu ◽  
Jared M. Brown ◽  
...  
Keyword(s):  
Liver Injury ◽  
Alcoholic Liver Injury ◽  
Hepatic Macrophages

Potential role of hepatic macrophages in neutrophil-mediated liver injury in rats with sepsis

Hepatology ◽  
1993 ◽  
Vol 17 (6) ◽  
pp. 1086-1094 ◽  
Author(s):  
Fukashi Doi ◽  
Tomomochi Goya ◽  
Motomichi Torisu
Keyword(s):  
Liver Injury ◽  
Potential Role ◽  
Hepatic Macrophages

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.

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