Golgi Apparatus-Targeted Chondroitin-Modified Nanomicelles Suppress Hepatic Stellate Cell Activation for the Management of Liver Fibrosis

Luo, Jingwen; Zhang, Pei; Zhao, Ting; Jia, Mengdi; Yin, Peng; Li, Wenhao; Zhang, Zhirong; Fu, Yao; Gong, Tao

doi:10.1021/acsnano.8b06924

Cited by 97 publications

(83 citation statements)

References 67 publications

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“…In addition, the production and liberation of TNF-α are predominantly regulated by the TLR4/NF-κB signaling pathway during liver inflammation (37). Accordingly, the inhibition of the TLR4/NF-κB signaling pathway can decrease TNF-α production, which is an effective strategy for FHF alleviation (38,39). In our study, MF suppressed TNF-α synthesis transcriptionally and translationally, as shown by the decrease in mRNA and protein of TNF-α after MF pretreatment in both mice and KCs.…”

Section: Discussionsupporting

confidence: 52%

Mangiferin Attenuates LPS/D-GalN-Induced Acute Liver Injury by Promoting HO-1 in Kupffer Cells

et al. 2020

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Acute liver injury and its terminal phase, hepatic failure, trigger a series of complications, including hepatic encephalopathy, systematic inflammatory response syndrome, and multiorgan failure, with relatively high morbidity and mortality. Liver transplantation is the ultimate intervention, but the shortage of donor organs has limited clinical success. Mangiferin (MF), a xanthone glucoside, has been reported to have excellent anti-inflammatory efficacy. Here, a lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury mouse model was established to investigate the protective role of MF and the underlying mechanisms of action. Pretreatment with MF improved survival, decreased serum aminotransferase activities, and inhibited hepatic TNF-α production in LPS/D-GalN-challenged mice. Through Kupffer cell (KC) deletion by GdCl 3 and KC adoptive transfer, KCs were confirmed to be involved in these beneficial effects of MF. MF reduced LPS-mediated TNF-α production via the suppression of the TLR4/NF-κB signaling pathway in vitro. MF promoted HO-1 expression, but the knockdown of HO-1 prevented TNF-α inhibition, suggesting that the damage-resistance effects of HO-1 occurred via the suppression of TNF-α synthesis. When HO-1-silenced KCs were transferred to the liver with KC deletion, the protective effect of MF against LPS/D-GalN-induced acute liver injury was reduced, illustrating the role of KC-derived HO-1 in the anti-injury effects of MF. Collectively, MF attenuated acute liver injury induced by LPS/D-GalN via the inhibition of TNF-α production by promoting KCs to upregulate HO-1 expression.

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Section: Discussionsupporting

confidence: 52%

Mangiferin Attenuates LPS/D-GalN-Induced Acute Liver Injury by Promoting HO-1 in Kupffer Cells

et al. 2020

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“…There have been a variety of experimental studies conducted targeting the ECM by different means to interfere with hepatic fibrosis. Chondroitin sulfate deoxycholic acid conjugates loaded with retinoic acid and doxorubicin were found accumulated within the Golgi apparatus and destroyed the production of collagen (70). Relaxin administration in well-established liver fibrosis model has shown to reduce collagen expression, α-SMA levels, and lowering liver enzymes (71).…”

Section: Reversal Of Fibrosis By Targeting the Extracellular Matrix: Novel Targets And Formulation-based Approachesmentioning

confidence: 99%

It’s all about the spaces between cells: role of extracellular matrix in liver fibrosis

Khurana¹,

Sayed²,

Allawadhi³

et al. 2021

Ann Transl Med

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Liver fibrosis is one of the leading complications of a variety of chronic liver disorders, including the nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, liver cirrhosis and liver failure. The progression of liver fibrosis is driven by chronic inflammation, which activates the secretory fibroblasts to the myofibroblast phenotype. These specialized liver cells are called as hepatic stellate cells (HSCs).The excessive extracellular matrix (ECM) secretion creates a large number of complications. Fibrosis is the result of imbalance between the matrix synthesizing and matrix degrading factors. The major ECM proteins include the matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), lysyl oxidases (LOX), lysyl oxidase-like (LOXLs) enzymes, tenascins and others. These ECM proteins present novel avenues for the therapeutics of liver fibrosis. The current review highlights the major role played by these critical matrix proteins in liver fibrosis. Further, some of the targeted formulations used against these proteins are discussed and suggestions are provided to select the course of research for successful clinical translation of basic research findings for the amelioration of liver fibrosis.

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“…103 Gong's team repeatedly proved that chondroitin sulfate (CS) nanomicelles targeted the Golgi since the glycosyltransferases in the Golgi could specifically bind to CS. 104,105 However, it should be pointed out that compared with the targeting of the mitochondria and nuclei, the subcellular targeting of the ER and Golgi is still in its infancy, with not enough information available to apply comprehensive design strategies.…”

Section: Er and Golgi Targeting Nanoformulationsmentioning

confidence: 99%

Precise design strategies of nanomedicine for improving cancer therapeutic efficacy using subcellular targeting

Shi

et al. 2020

Sig Transduct Target Ther

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Therapeutic efficacy against cancer relies heavily on the ability of the therapeutic agents to reach their final targets. The optimal targets of most cancer therapeutic agents are usually biological macromolecules at the subcellular level, which play a key role in carcinogenesis. Therefore, to improve the therapeutic efficiency of drugs, researchers need to focus on delivering not only the therapeutic agents to the target tissues and cells but also the drugs to the relevant subcellular structures. In this review, we discuss the most recent construction strategies and release patterns of various cancer cell subcellular-targeting nanoformulations, aiming at providing guidance in the overall design of precise nanomedicine. Additionally, future challenges and potential perspectives are illustrated in the hope of enhancing anticancer efficacy and accelerating the translational progress of precise nanomedicine.

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Golgi Apparatus-Targeted Chondroitin-Modified Nanomicelles Suppress Hepatic Stellate Cell Activation for the Management of Liver Fibrosis

Cited by 97 publications

References 67 publications

Mangiferin Attenuates LPS/D-GalN-Induced Acute Liver Injury by Promoting HO-1 in Kupffer Cells

Mangiferin Attenuates LPS/D-GalN-Induced Acute Liver Injury by Promoting HO-1 in Kupffer Cells

It’s all about the spaces between cells: role of extracellular matrix in liver fibrosis

Precise design strategies of nanomedicine for improving cancer therapeutic efficacy using subcellular targeting

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