Dataset Information

Macrophage-derived exosomal miR-155 regulating hepatocyte pyroptosis in MAFLD.

ABSTRACT:

Background

Previous studies have shown that pyroptosis in hepatocyte is essential for the development of MAFLD. Growing evidence has shown that exosomal miRNAs-mediated communication between inflammatory cells and hepatocyte is an important link in MAFLD. In the present study, we aim to elucidate whether macrophage-derived exosomal miRNAs contribute to the hepatocyte pyroptosis in the pathophysiological process of MAFLD.

Methods

The effects of hepatocyte pyroptosis were investigated in an HFD-induced MAFLD mouse model and in the liver tissues from patients with MAFLD using immunohistochemistry, real-time PCR, Western blotting, and luciferase reporter assay, among other techniques. MiR-155 inhibitor tail injections and AAV-FoxO3a-GFP were also administered to respectively inhibit or overexpress its expression in an HFD-induced MAFLD mouse model.

Results

Hepatocyte pyroptosis was heightened in the liver tissue of patients with MAFLD or HFD-induced MAFLD mouse. Importantly, treatment with a caspase-1 inhibitor or overexpression of FoxO3a reversed this trend. Our study also demonstrated that miR-155 expression and the number of infiltrated macrophages were increased, and knockdown of miR-155 attenuated hepotocyte pyroptosis and liver fibrosis in HFD-induced mouse. In addition, we demonstrated that macrophage-derived exosomal miR-155 was transferred to hepatocytes, leading to hepatocyte pyroptosis in MAFLD mouse. Furthermore, blockade of exosome secretion improved hepotocyte pyroptosis and liver fibrosis in HFD-induced mouse. On the contrary, macrophage-derived exosomal miR-155 worsened hepotocyte pyroptosis. Moreover, we found that miR-155 promoted hepatocyte pyroptosis in MAFLD by down-regulating FoxO3a.

Conclusions

Taken together, our results demonstrated that macrophage-derived exosomal miR-155 promotes hepatocyte pyroptosis and liver fibrosis in MAFLD.

SUBMITTER: He W

PROVIDER: S-EPMC11328038 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Macrophage-derived exosomal miR-155 regulating hepatocyte pyroptosis in MAFLD.

He Wei W Xu Jin J Wang Xiang X Fan Zhining Z Li Hai H

Heliyon 20240725 15

<h4>Background</h4>Previous studies have shown that pyroptosis in hepatocyte is essential for the development of MAFLD. Growing evidence has shown that exosomal miRNAs-mediated communication between inflammatory cells and hepatocyte is an important link in MAFLD. In the present study, we aim to elucidate whether macrophage-derived exosomal miRNAs contribute to the hepatocyte pyroptosis in the pathophysiological process of MAFLD.<h4>Methods</h4>The effects of hepatocyte pyroptosis were investigat ...[more]

PMID: 39157367

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Dataset Information

Macrophage-derived exosomal miR-155 regulating hepatocyte pyroptosis in MAFLD.

Background

Methods

Results

Conclusions

Publications

Macrophage-derived exosomal miR-155 regulating hepatocyte pyroptosis in MAFLD.

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