MiR-690 treatment causes decreased fibrosis and steatosis and restores specific Kupffer cell functions in NASH

Gao, Hong; Jin, Zhongmou; Bandyopadhyay, Gautam; Rocha, Karina Cunha e; Liu, Xiao; Zhao, Huayi; Zhang, Dinghong; Jouihan, Hani; Pourshahian, Soheil; Kisseleva, Tatiana; Brenner, David A.; Ying, Wei; Olefsky, Jerrold M.

doi:10.1016/j.cmet.2022.05.008

Cited by 69 publications

(49 citation statements)

References 47 publications

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“…Under homeostatic conditions, the hepatic macrophage population contains only a small amount of MoMFs. KCs could directly inhibit the inflammatory response of MoMFs by secreting miR-690-containing exosomes, whereas miR-690 of KCs showed low expression during the progression of NASH ( 36 ), which might promote the recruitment and pro-inflammatory transformation of MoMFs. In addition, activated KCs can promote the recruitment of Ly6C hi MoMFs by secreting CCL2 ( 31 ).…”

Section: Effect Of Macrophages On the Inflammatory Response In Nafldmentioning

confidence: 99%

Programmed cell death and lipid metabolism of macrophages in NAFLD

et al. 2023

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Non-alcoholic fatty liver disease (NAFLD) has now become the leading chronic liver disease worldwide with lifestyle changes. This may lead to NAFLD becoming the leading cause of end-stage liver disease in the future. To date, there are still no effective therapeutic drugs for NAFLD. An in-depth exploration of the pathogenesis of NAFLD can help to provide a basis for new therapeutic agents or strategies. As the most important immune cells of the liver, macrophages play an important role in the occurrence and development of liver inflammation and are expected to become effective targets for NAFLD treatment. Programmed cell death (PCD) of macrophages plays a regulatory role in phenotypic transformation, and there is also a certain connection between different types of PCD. However, how PCD regulates macrophage polarization has still not been systematically elucidated. Based on the role of lipid metabolic reprogramming in macrophage polarization, PCD may alter the phenotype by regulating lipid metabolism. We reviewed the effects of macrophages on inflammation in NAFLD and changes in their lipid metabolism, as well as the relationship between different types of PCD and lipid metabolism in macrophages. Furthermore, interactions between different types of PCD and potential therapeutic agents targeting of macrophages PCD are also explored.

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Section: Effect Of Macrophages On the Inflammatory Response In Nafldmentioning

confidence: 99%

Programmed cell death and lipid metabolism of macrophages in NAFLD

et al. 2023

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“…During the development of NASH, KCs become miR-690 deficient, and miR-690 levels are markedly lower in mouse and human NASH livers than in the controls. KC-specific knockout of miR-690 promotes NASH pathogenesis [ 44 ]. In addition, adipocyte-derived EVs have been demonstrated to promote hepatic inflammation via monocyte chemoattractant protein-1and IL-6 [ 45 ] and contribute to fibrosis via alteration of TIMPs and MMPs expression in hepatocytes and HSCs [ 46 ].…”

Section: Role Of Extracellular Vesicles and Exosomes In Nash Pathogen...mentioning

confidence: 99%

“…When a miR-690 mimic is administered to NASH mice in vivo, all the features of the NASH phenotype are robustly inhibited. These studies show that KCs may play a central role in the etiology of NASH and raise the possibility that miR-690 could emerge as a therapeutic potential for this condition [ 44 ].…”

Section: Potential Roles Of Exosomal Mirnas In Diagnosis and Treatmen...mentioning

confidence: 99%

Exosomal microRNAs and Progression of Nonalcoholic Steatohepatitis (NASH)

Lai

2022

IJMS

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Nonalcoholic fatty liver disease (NAFLD)/metabolic associated fatty liver disease (MAFLD) is becoming a public health problem worldwide. Steatosis as the simple form and nonalcoholic steatohepatitis (NASH) as its progression form are commonly seen in liver biopsy specimens from patients with obesity, diabetes, hyperlipidemia, hypertension, and the use of certain drugs. Patients with NASH and advanced fibrosis were associated with increased risks of liver-related complications, including hepatocellular carcinoma (HCC). However, the mechanisms regarding the progression from simple steatosis to NASH fibrosis remain incompletely understood. Because NASH-caused liver injury is a complex process and multiple cell types are involved, intercellular communication is likely mediated by extracellular vesicles. Exosomes are a type of small extracellular vesicles and contain various cellular molecules, including proteins, messenger RNAs (mRNAs), and microRNAs (miRNAs). MiRNAs are short, non-coding RNA species that are important post-transcriptional regulators of gene expression and may play an important role in the pathogenesis of NALFD/NASH. In this article, we review the articles about NASH and exosomal miRNAs published in the most recent English literature through PubMed search and discuss the most recent criteria for histological diagnosis, pathogenesis from steatosis to NASH, roles of exosomal miRNAs in NASH pathogenesis and progression, as well as their potential in future clinical diagnosis and treatment for patients with NASH.

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“…MicroRNAs (miRNAs or miRs) play a key role in cancer and inflammation, but their role in NASH still needs to be explored. MiR-690 treatment has been reported to reduce fibrosis and steatosis in NASH [23] and restore specific kuffer cell function. Inhibition of miR-188-5p also significantly reduced HSC activation and proliferation via the PTEN/PI3K/AKT pathway, thereby inhibiting liver fibrosis [24].…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rg1 attenuates the NASH phenotype by regulating the miR-375-3p/ATG2B/PTEN-AKT axis to mediate autophagy and pyroptosis

et al. 2023

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Background Nonalcoholic steatohepatitis (NASH) is one of the most frequent liver diseases at present, and there is no radical treatment. The consequences of a variety of ginsenoside compounds on this situation have before been reported, however, the specific effect on the monomeric ginsenoside Rg1 (Rg1) and its associated underlying molecular mechanism stay unknown. Material and methods In vitro, the cell models were constructed by exposing free fatty acids (FFAs) to HepG2 cells. A methionine and choline deficiency (MCD)-induced NASH mouse model was also established over 5–6 weeks of treatment. Rg1 is a traditional Chinese medicine monomer. These NASH models were treated with Rg1 and analyzed by qRT-PCR, Western Blot, sequencing, Oil red O staining, immunofluorescence, enzyme activity, HE staining, ELISA, double luciferase reporter assay, and immunohistochemistry. Results Overexpression of ATG2B, an autophagy-related protein, attenuated lipid droplet accumulation and reduces ALT, AST, inflammatory cytokines, hydrogen peroxide, and pyroptosis in established mouse and cellular models of NASH and increased levels of ATP and autophagy. The binding sites of miR-375-3p and ATG2B were verified by bioinformatic prediction and a dual-luciferase reporter gene. Knockdown of miR-375-3p promoted autophagy and inhibited pyroptosis. ATG2B knockdown substantially attenuated the impact of miR-375-3p on NASH. Rg1 appears to regulate the occurrence and development of NASH inflammation through miR-375-3p and ATG2B in vitro and in vivo, and is regulated by PTEN-AKT pathway. Conclusions This study showed that Rg1 participates in autophagy and pyroptosis through the miR-375-3p/ATG2B/PTEN-AKT pathway, thereby alleviating the occurrence and development of NASH, for that reason revealing Rg1 as a candidate drug for NASH.

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MiR-690 treatment causes decreased fibrosis and steatosis and restores specific Kupffer cell functions in NASH

Cited by 69 publications

References 47 publications

Programmed cell death and lipid metabolism of macrophages in NAFLD

Programmed cell death and lipid metabolism of macrophages in NAFLD

Exosomal microRNAs and Progression of Nonalcoholic Steatohepatitis (NASH)

Ginsenoside Rg1 attenuates the NASH phenotype by regulating the miR-375-3p/ATG2B/PTEN-AKT axis to mediate autophagy and pyroptosis

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