AMSC-derived exosomes alleviate lipopolysaccharide/d-galactosamine-induced acute liver failure by miR-17-mediated reduction of TXNIP/NLRP3 inflammasome activation in macrophages

Liu, Yanning; Lou, Guohua; Li, Aichun; Zhang, Tianbao; Qi, Jinjin; Ye, Dan; Zheng, Min; Chen, Zhi

doi:10.1016/j.ebiom.2018.08.054

Cited by 172 publications

(122 citation statements)

References 38 publications

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“…Additionally, it has been shown that exosomes derived from alcoholic hepatocytes transferred miRNA-122 to macrophages, increased expression of pro-inflammatory cytokines, and sensitized monocytes to LPS stimulation [52]. Furthermore, mesenchymal stem cell-derived exosomal miR-17 reduced inflammatory factor secretion by suppressing inflammasome activation in hepatic macrophages [53]. However, the role of cholangiocyte-derived exosomes in the regulation of hepatic macrophages remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Cholangiocyte-Derived Exosomal lncRNA H19 Promotes Macrophage Activation and Hepatic Inflammation under Cholestatic Conditions

Liu

Wang

et al. 2020

Cells

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Activation of hepatic macrophages represents the critical driving force to promote cholestatic liver injury. Exosomes, as important small extracellular vesicles released by almost all types of cells, contribute to intercellular communication. We previously reported that cholangiocyte-derived exosomal long noncoding RNA (lncRNA) H19 plays a vital role in disrupting bile acid homeostasis in hepatocytes and promoting the activation of hepatic stellate cells (HSCs). Exosomal H19 derived from cholangiocytes was rapidly taken up by Kupffer cells. However, the mechanistic links between exosomal lncRNA H19 and macrophage-driven inflammation in cholestasis remain unclear. Here, we reported that the hepatic H19 level was closely correlated with macrophage activation and hepatic fibrosis in both Mdr2-/- and bile duct ligation (BDL) cholestatic mouse models, as well as in human primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) patients. Exosomal H19 significantly induced the expression and secretion of chemokine (C–C motif) ligand 2 (CCL-2) and interleukin 6 (IL-6) in Kupffer cells. H19-enriched exosomes enhanced the activation M1 polarization of Kupffer cells and promoted the recruitment and differentiation of bone marrow-derived macrophages, which were inhibited by a CCL-2 pharmacological inhibitor. In conclusion, Cholangiocyte-derived exosomal H19 played a critical role in macrophage activation, differentiation, and chemotaxis through CCL-2/CCR-2 signaling pathways, which represent a therapeutic target for cholestatic liver diseases.

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Section: Discussionmentioning

confidence: 99%

Cholangiocyte-Derived Exosomal lncRNA H19 Promotes Macrophage Activation and Hepatic Inflammation under Cholestatic Conditions

Liu

Wang

et al. 2020

Cells

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“…As shown in Table 2 (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46), recent findings depicted that MSC-derived exosomes deliver various cytoplasmatic constituents of the MSC secretomes, relevant to the stemness, angiogenesis, and particularly inflammatory factors. They were first used in 2010 for regeneration of tissues in a mouse model of myocardial ischemia/reperfusion injury (47) and are extensively on investigations at present.…”

Section: Msc-derived Exosome Therapy: Cons and Prosmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Ace Card to Address Autoimmune Diseases

Baharlooi

Azimi

Salehi

et al. 2020

IJSC

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With the development of novel treatments for autoimmune disorders, it has become a popular research focus which mesenchymal stem cells (MSCs) have the capacity to counteract with autoimmune diseases progression. One of the underlying mechanisms behind their activities is the release of extracellular vesicles especially exosomes. MSC-derived exosomes are hypoimmunogenic nanocarriers which contain numerous immunoregulatory factors and similar to other exosomes, are able to pass through boundaries like the blood-brain barrier (BBB). Accumulating evidence provided by animal studies has demonstrated that MSC-derived exosomes, as a novel therapy, can re-induce self-tolerance, without subsequent complications reported for other treatments. Therefore, therapeutic applications of MSC-derived exosomes are contributing to core advances in the field of autoimmune diseases. Here, we briefly describe the biological characteristics of MSC-derived exosomes and review the experimentally verified outcomes for autoimmune disease therapy purposes.

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“…The nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome has been found to play a critical role in GalN/LPS-induced acute liver injury in mice. mRNA and protein levels of the Nlrp3 gene are increased in mice after GalN/LPS challenge [8,9], and inhibition of the NLRP3 inflammasome with its specific inhibitor MCC950 ameliorates the severity of GalN/LPS-induced acute liver injury in mice [6].…”

Section: Introductionmentioning

confidence: 99%

Protective Role of Shiitake Mushroom-Derived Exosome-Like Nanoparticles in D-Galactosamine and Lipopolysaccharide-Induced Acute Liver Injury in Mice

Liu

Chen

et al. 2020

Nutrients

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Fulminant hepatic failure (FHF) is a rare, life-threatening liver disease with a poor prognosis. Administration of D-galactosamine (GalN) and lipopolysaccharide (LPS) triggers acute liver injury in mice, simulating many clinical features of FHF in humans; therefore, this disease model is often used to investigate potential therapeutic interventions to treat FHF. Recently, suppression of the nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome, was shown to alleviate the severity of GalN/LPS-induced liver damage in mice. Therefore, the goal of this study was to find dietary exosome-like nanoparticles (ELNs) with therapeutic potential in curbing FHF by suppressing the NLRP3 inflammasome. Seven commonly consumed mushrooms were used to extract ELNs. These mushrooms were found to contain ELNs composed of RNAs, proteins, and lipids. Among these mushroom-derived ELNs, only shiitake mushroom-derived ELNs (S-ELNs) substantially inhibited NLRP3 inflammasome activation by preventing inflammasome formation in primary macrophages. S-ELNs also suppressed the secretion of interleukin (IL)-6, as well as both protein and mRNA levels of the Il1b gene. Remarkably, pre-treatment with S-ELNs protected mice from GalN/LPS-induced acute liver injury. Therefore, S-ELNs, identified as potent new inhibitors of the NLRP3 inflammasome, represent a promising class of agents with the potential to combat FHF.

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AMSC-derived exosomes alleviate lipopolysaccharide/d-galactosamine-induced acute liver failure by miR-17-mediated reduction of TXNIP/NLRP3 inflammasome activation in macrophages

Cited by 172 publications

References 38 publications

Cholangiocyte-Derived Exosomal lncRNA H19 Promotes Macrophage Activation and Hepatic Inflammation under Cholestatic Conditions

Cholangiocyte-Derived Exosomal lncRNA H19 Promotes Macrophage Activation and Hepatic Inflammation under Cholestatic Conditions

Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Ace Card to Address Autoimmune Diseases

Protective Role of Shiitake Mushroom-Derived Exosome-Like Nanoparticles in D-Galactosamine and Lipopolysaccharide-Induced Acute Liver Injury in Mice

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