Single-cell RNA seq identifies Plg-RKT-PLG as signals inducing phenotypic transformation of scar-associated macrophage in liver fibrosis

Yang, Yang; Li, Weiyang; Liu, Chang; Liu, Fei; Yang, Lin; Yue, Wenhui; Yang, Le; Xue, Renmin; Zhang, Kai; Zhang, Hang; Chang, Na; Li, Liying

doi:10.1016/j.bbadis.2023.166754

Cited by 3 publications

(1 citation statement)

References 59 publications

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“…The C 60 nanofilm increased the expression of NR2F6, which, according to the literature, correlates with NASH and intensifies the production of cytokines. On the other hand, the C 60 nanofilm also upregulated the transmembrane plasminogen receptor, a deficiency of which in mice fed a high-fat diet caused weight gain, fatty liver and insulin resistance [68]. Fullerene appears to have an anti-inflammatory effect by targeting the nuclear factor κB (NF-κB) transcription factor pathway, which is responsible for inflammation-induced cell death [69].…”

Section: Discussionmentioning

confidence: 99%

Influence of C60 Nanofilm on the Expression of Selected Markers of Mesenchymal–Epithelial Transition in Hepatocellular Carcinoma

Sosnowska,

Kutwin,

Zawadzka

et al. 2023

Cancers

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The epithelial–mesenchymal transition (EMT) is a process in which epithelial cells acquire the ability to actively migrate via a change to the mesenchymal phenotype. This mechanism occurs in an environment rich in cytokines and reactive oxygen species but poor in nutrients. The aim of this study was to demonstrate that the use of a fullerene C60 nanofilm can inhibit liver cancer cell invasion by restoring their non-aggressive, epithelial phenotype. We employed epithelial and mesenchymal HepG2 and SNU-449 liver cancer cells and non-cancerous mesenchymal HFF2 cells in this work. We used enzyme-linked immunosorbent assays (ELISAs) to determine the content of glutathione and transforming growth factor (TGF) in cells. We measured the total antioxidant capacity with a commercially available kit. We assessed cell invasion based on changes in morphology, the scratch test and the Boyden chamber invasion. In addition, we measured the effect of C60 nanofilm on restoring the epithelial phenotype at the protein level with protein membranes, Western blotting and mass spectrometry. C60 nanofilm downregulated TGF and increased glutathione expression in SNU-449 cells. When grown on C60 nanofilm, invasive cells showed enhanced intercellular connectivity; reduced three-dimensional invasion; and reduced the expression of key invasion markers, namely MMP-1, MMP-9, TIMP-1, TIMP-2 and TIMP-4. Mass spectrometry showed that among the 96 altered proteins in HepG2 cells grown on C60 nanofilm, 41 proteins are involved in EMT and EMT-modulating processes such as autophagy, inflammation and oxidative stress. The C60 nanofilm inhibited autophagy, showed antioxidant and anti-inflammatory properties, increased glucose transport and regulated the β-catenin/keratin/Smad4/snail+slug and MMP signalling pathways. In conclusion, the C60 nanofilm induces a hybrid mesenchymal–epithelial phenotype and could be used in the prevention of postoperative recurrences.

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Section: Discussionmentioning

confidence: 99%

Influence of C60 Nanofilm on the Expression of Selected Markers of Mesenchymal–Epithelial Transition in Hepatocellular Carcinoma

Sosnowska,

Kutwin,

Zawadzka

et al. 2023

Cancers

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An Autologous Macrophage‐Based Phenotypic Transformation‐Collagen Degradation System Treating Advanced Liver Fibrosis

Duan,

Liu,

et al. 2023

Advanced Science

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In advanced liver fibrosis (LF), macrophages maintain the inflammatory environment in the liver and accelerate LF deterioration by secreting proinflammatory cytokines. However, there is still no effective strategy to regulate macrophages because of the difficulty and complexity of macrophage inflammatory phenotypic modulation and the insufficient therapeutic efficacy caused by the extracellular matrix (ECM) barrier. Here, AC73 and siUSP1 dual drug‐loaded lipid nanoparticle is designed to carry milk fat globule epidermal growth factor 8 (MFG‐E8) (named MUA/Y) to effectively inhibit macrophage proinflammatory signals and degrade the ECM barrier. MFG‐E8 is released in response to the high reactive oxygen species (ROS) environment in LF, transforming macrophages from a proinflammatory (M1) to an anti‐inflammatory (M2) phenotype and inducing macrophages to phagocytose collagen. Collagen ablation increases AC73 and siUSP1 accumulation in hepatic stellate cells (HSCs) and inhibits HSCs overactivation. Interestingly, complete resolution of liver inflammation, significant collagen degradation, and HSCs deactivation are observed in methionine choline deficiency (MCD) and CCl4 models after tail vein injection of MUA/Y. Overall, this work reveals a macrophage‐focused regulatory treatment strategy to eliminate LF progression at the source, providing a new perspective for the clinical treatment of advanced LF.

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Jiawei Taohe Chengqi decoction inhibition of the notch signal pathway affects macrophage reprogramming to inhibit HSCs activation for the treatment of hepatic fibrosis

Shao,

Xu,

Sun

et al. 2024

Journal of Ethnopharmacology

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Single-cell RNA seq identifies Plg-RKT-PLG as signals inducing phenotypic transformation of scar-associated macrophage in liver fibrosis

Cited by 3 publications

References 59 publications

Influence of C60 Nanofilm on the Expression of Selected Markers of Mesenchymal–Epithelial Transition in Hepatocellular Carcinoma

Influence of C60 Nanofilm on the Expression of Selected Markers of Mesenchymal–Epithelial Transition in Hepatocellular Carcinoma

An Autologous Macrophage‐Based Phenotypic Transformation‐Collagen Degradation System Treating Advanced Liver Fibrosis

Jiawei Taohe Chengqi decoction inhibition of the notch signal pathway affects macrophage reprogramming to inhibit HSCs activation for the treatment of hepatic fibrosis

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