M2 macrophage-derived exosomal microRNA-411-5p impedes the activation of hepatic stellate cells by targeting CAMSAP1 in NASH model

Wan, Zhang; Yang, Xiaoàn; Liu, Xiaoquan; Sun, Yinfang; Yu, Piaojian; Xu, Fen; Deng, Hong

doi:10.1016/j.isci.2022.104597

Cited by 28 publications

(12 citation statements)

References 48 publications

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“…29,30 The mechanistic link between loss of lipids in HSCs and cell activation is not well understood, but is thought to involve remarkable influence of the molecular and cellular pathways in hepatic inflammatory microenvironment. [30][31][32] Cellular crosstalk between HSCs and surrounding multiple tissue-resident cells, 33,34 including macrophages, 35,36 neutrophils, 37,38 platelets, 33,39 dendritic cells, 40 sinusoidal endothelial cells, 41,42 epithelial cells, 43 natural killer cells, 44,45 various T lymphocytes, 46,47 and B cells, 48,49 promotes or inhibits the activation of HSCs. For example, inflammation induced by liver injury triggers the recruitment of macrophages to the liver, where they produce cytokines and chemokines, such as TGF-β, platelet-derived growth factor (PDGF), tumor necrosis factor-alpha (TNF-α), IL-1β, oncostatin M (OSM), chemokine ligand 3/5 (CCL3/5), directly inducing HSC activation, and subsequently forming a definitely complex activation network.…”

Section: Mechanism Of Hsc Activationmentioning

confidence: 99%

“…Thus, an exosomal miR-411-5p inhibitor may serve as a potential therapeutic target for NAFLD and fibrosis. 35 Similarly, through targeting HSCs, several exosomal microRNAs originating from other cell types, such as liver stem cells (miR-141-3p 151 and miR-146a-5p 132 ) and hepatocytes (miRNA-26b, 152 miRNA-107, 153 and miR-19a 102 ) have biological effects that influence the fibrogenic phenotype of HSCs.…”

Section: Clinical Value Of Hsc-derived Exosomes In Liver Diseasesmentioning

confidence: 99%

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Unraveling the Emerging Niche Role of Hepatic Stellate Cell-derived Exosomes in Liver Diseases

Yin¹,

Li²,

Song³

et al. 2022

J Clin Transl Hepatol

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Hepatic stellate cells (HSCs) play an essential role in various liver diseases, and exosomes are critical mediators of intercellular communication in local and distant microenvironments. Cellular crosstalk between HSCs and surrounding multiple tissue-resident cells promotes or inhibits the activation of HSCs. Substantial evidence has revealed that HSC-derived exosomes are involved in the occurrence and development of liver diseases through the regulation of retinoid metabolism, lipid metabolism, glucose metabolism, protein metabolism, and mitochondrial metabolism. HSCderived exosomes are underpinned by vehicle molecules, such as mRNAs and microRNAs, that function in, and significantly affect, the processes of various liver diseases, such as acute liver injury, alcoholic liver disease, nonalcoholic fatty liver disease, viral hepatitis, fibrosis, and cancer. As such, numerous exosomes derived from HSCs or HSCassociated exosomes have attracted attention because of their biological roles and translational applications as potential targets for therapeutic targets. Herein, we review the pathophysiological and metabolic processes associated with HSC-derived exosomes, their roles in various liver diseases and their potential clinical application.

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Section: Mechanism Of Hsc Activationmentioning

confidence: 99%

Section: Clinical Value Of Hsc-derived Exosomes In Liver Diseasesmentioning

confidence: 99%

Unraveling the Emerging Niche Role of Hepatic Stellate Cell-derived Exosomes in Liver Diseases

Yin¹,

Li²,

Song³

et al. 2022

J Clin Transl Hepatol

View full text Add to dashboard Cite

show abstract

“…Wan et al. found that miR-411-5p delivered by exosomes of M2 macrophages could inhibit HSC activation in a nonalcoholic steatohepatitis model, which was associated with the downregulation of Calmodulin-Regulated Spectrin-Associated Protein by miR-411-5p ( 61 ). Another study found that after binding to relaxin, hepatic macrophages could mediate the inactivation of aHSC via miR-30a-5p in their released exosomes ( 62 ).…”

Section: Exosomes In Lf Pathogenesismentioning

confidence: 99%

Exosomes in liver fibrosis: The role of modulating hepatic stellate cells and immune cells, and prospects for clinical applications

Liu

Yang

et al. 2023

Front. Immunol.

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Liver fibrosis is a global health problem caused by chronic liver injury resulting from various factors. Hepatic stellate cells (HSCs) have been found to play a major role in liver fibrosis, and pathological stimuli lead to their transdifferentiation into myofibroblasts. Complex multidirectional interactions between HSCs, immune cells, and cytokines are also critical for the progression of liver fibrosis. Despite the advances in treatments for liver fibrosis, they do not meet the current medical needs. Exosomes are extracellular vesicles of 30-150 nm in diameter and are capable of intercellular transport of molecules such as lipids, proteins and nucleic acids. As an essential mediator of intercellular communication, exosomes are involved in the physiological and pathological processes of many diseases. In liver fibrosis, exosomes are involved in the pathogenesis mainly by regulating the activation of HSCs and the interaction between HSCs and immune cells. Serum-derived exosomes are promising biomarkers of liver fibrosis. Exosomes also have promising therapeutic potential in liver fibrosis. Exosomes derived from mesenchymal stem cells and other cells exhibit anti-liver fibrosis effects. Moreover, exosomes may serve as potential therapeutic targets for liver fibrosis and hold promise in becoming drug carriers for liver fibrosis treatment.

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“…Further investigation revealed that exosomal miR-411-5p from M2 macrophages could inhibit the activation of HSCs. Additionally, miR-411-5p was found to directly downregulate the expression of Calmodulin-Regulated Spectrin-Associated Protein 1 ( CAMSAP1 ) to inactivate HSCs ( 114 ). CCl4-induced liver fibrosis model, exosomes derived from relaxin-treated macrophages exhibited a potent antifibrogenic effect, which was primarily attributed to miR-30a-5p ( 115 ).…”

Section: The Role Of Mirnas and Macrophages In Liver Fibrosismentioning

confidence: 99%

MicroRNA: role in macrophage polarization and the pathogenesis of the liver fibrosis

Wang

et al. 2023

Front. Immunol.

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Macrophages, as central components of innate immunity, feature significant heterogeneity. Numerus studies have revealed the pivotal roles of macrophages in the pathogenesis of liver fibrosis induced by various factors. Hepatic macrophages function to trigger inflammation in response to injury. They induce liver fibrosis by activating hepatic stellate cells (HSCs), and then inflammation and fibrosis are alleviated by the degradation of the extracellular matrix and release of anti-inflammatory cytokines. MicroRNAs (miRNAs), a class of small non-coding endogenous RNA molecules that regulate gene expression through translation repression or mRNA degradation, have distinct roles in modulating macrophage activation, polarization, tissue infiltration, and inflammation regression. Considering the complex etiology and pathogenesis of liver diseases, the role and mechanism of miRNAs and macrophages in liver fibrosis need to be further clarified. We first summarized the origin, phenotypes and functions of hepatic macrophages, then clarified the role of miRNAs in the polarization of macrophages. Finally, we comprehensively discussed the role of miRNAs and macrophages in the pathogenesis of liver fibrotic disease. Understanding the mechanism of hepatic macrophage heterogeneity in various types of liver fibrosis and the role of miRNAs on macrophage polarization provides a useful reference for further research on miRNA-mediated macrophage polarization in liver fibrosis, and also contributes to the development of new therapies targeting miRNA and macrophage subsets for liver fibrosis.

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M2 macrophage-derived exosomal microRNA-411-5p impedes the activation of hepatic stellate cells by targeting CAMSAP1 in NASH model

Cited by 28 publications

References 48 publications

Unraveling the Emerging Niche Role of Hepatic Stellate Cell-derived Exosomes in Liver Diseases

Unraveling the Emerging Niche Role of Hepatic Stellate Cell-derived Exosomes in Liver Diseases

Exosomes in liver fibrosis: The role of modulating hepatic stellate cells and immune cells, and prospects for clinical applications

MicroRNA: role in macrophage polarization and the pathogenesis of the liver fibrosis

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