Proteomic Changes of Activated Hepatic Stellate Cells

Schinagl, Maximilian; Tomin, Tamara; Gindlhuber, Juergen; Honeder, Sophie; Pfleger, Raphael; Schittmayer, Matthias; Trauner, Michael; Birner‐Gruenberger, Ruth

doi:10.3390/ijms222312782

Cited by 10 publications

(6 citation statements)

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“…Quiescent hepatic stellate cells (qHSCs) are identified with lipid-rich vacuoles that store vitamin A in the form of retinyl ester, and play a critical role in the regulation of immune modulation, regeneration and lipid metabolism [ 7 ]. When the liver is damaged, qHSCs are activated and differentiate to a myofibroblast-like phenotype, and lose their lipid droplets (LDs) and their expression of α-smooth muscle actin (α-SMA) and type I collagen (Col I) [ 8 , 9 ]. The good plasticity of HSCs lies in the fact that the activated phenotype can undergo morphologic and biochemical reversal to a quiescent state [ 8 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…When the liver is damaged, qHSCs are activated and differentiate to a myofibroblast-like phenotype, and lose their lipid droplets (LDs) and their expression of α-smooth muscle actin (α-SMA) and type I collagen (Col I) [ 8 , 9 ]. The good plasticity of HSCs lies in the fact that the activated phenotype can undergo morphologic and biochemical reversal to a quiescent state [ 8 , 10 ]. Thus, aHSCs have become attractive therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

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Huc-MSC-derived exosomes modified with the targeting peptide of aHSCs for liver fibrosis therapy

Yan

Bai

et al. 2022

J Nanobiotechnol

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Background Effective therapeutics to stop or reverse liver fibrosis have not emerged, because these potential agents cannot specifically target activated hepatic stellate cells (aHSCs) or are frequently toxic to parenchymal cells. Human umbilical cord mesenchymal stem cell (Huc-MSC)-derived exosomes show promise in nanomedicine for the treatment of liver fibrosis. However, systemic injection showed that unmodified exosomes were mainly taken up by the mononuclear phagocyte system. The discovery of ligands that selectively bind to a specific target plays a crucial role in clinically relevant diagnostics and therapeutics. Herein, we aimed to identify the targeting peptide of aHSCs by screening a phage-displayed peptide library, and modify Huc-MSC-derived exosomes with the targeting peptide. Results In this study, we screened a phage-displayed peptide library by biopanning for peptides preferentially bound to HSC-T6 cells. The identified peptide, HSTP1, also exhibited better targeting ability to aHSCs in pathological sections of fibrotic liver tissues. Then, HSTP1 was fused with exosomal enriched membrane protein (Lamp2b) and was displayed on the surface of exosomes through genetic engineering technology. The engineered exosomes (HSTP1-Exos) could be more efficiently internalized by HSC-T6 cells and outperformed both unmodified exosomes (Blank-Exos) and Lamp2b protein overexpressed exosomes (Lamp2b + Exos) in enhancing the ability of exosomes to promote HSC-T6 reversion to a quiescent phenotype. In vivo results showed HSTP1-Exos could specifically target to the aHSC region after intravenous administration, as demonstrated by coimmunofluorescence with the typical aHSCs marker α-SMA, and enhance the therapeutic effect on liver fibrosis. Conclusion These results suggest that HSTP1 is a reliable targeting peptide that can specifically bind to aHSCs and that HSTP1-modified exosomes realize the precise treatment for aHSCs in complex liver tissue. We provide a novel strategy for clinical liver fibrosis therapy. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Huc-MSC-derived exosomes modified with the targeting peptide of aHSCs for liver fibrosis therapy

Yan

Bai

et al. 2022

J Nanobiotechnol

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“…during HSC activation, ribosomal proteins, proteins associated with cell cycle control and migration and other factors increase, as observed in an HSC activation model using immortalised human LX-2 HSCs and fetal bovine serum. 8 All these cellular processes contribute to the local accumulation of ECM, ultimately leading to scar formation in injured areas of the liver. If the profibrogenic triggers cease, fibrosis can regress.…”

Section: Open Accessmentioning

confidence: 99%

Extracellular vesicles targeting non-parenchymal cells: the therapeutical effect on liver fibrosis

Liu,

Wang

2024

egastro

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Liver fibrosis is the formation of a fibrous scar due to chronic liver disease including viral hepatitis, alcohol and non-alcoholic fatty liver disease. Without treatment, it will develop into cirrhosis and hepatocellular carcinoma. Up to now, there is no effective way to cure liver fibrosis. Extracellular vesicles (EVs) are biological nanoparticles with potential to be therapeutical agents or delivery tools. A lot of studies have demonstrated the therapeutical effect of EVs on liver fibrosis. In this review, we mainly pay attention to roles of liver non-parenchymal cells in pathology of fibrosis, the basic information about EVs and therapeutical effect on liver fibrosis of EVs when they act on non-parenchymal cells.

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“…7,[32][33][34] were kindly provided by the State Key Laboratory of Biotherapy, Sichuan University (Chengdu, China).…”

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confidence: 99%

Combined Amphiphilic Silybin Meglumine Nanosuspension Effective Against Hepatic Fibrosis in Mice Model

Yang,

Tan,

et al. 2023

IJN

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Introduction: Silybin (SLB) as an effective hepatoprotective phytomedicine has been limited by its hydrophobicity, poor bioavailability and accumulation at lesion sites. Additionally, present drug loading methods are impeded by their low drug loading capacity, potential hazard of materials and poor therapeutic effects. Consequently, there is a pressing need to devise an innovative approach for preparing nanosuspensions loaded with both SLB and Silybin Meglumine salt (SLB-M), as well as to investigate the therapeutic effects of SLB nanosuspensions against hepatic fibrosis. Methods: The SLB nanosuspension (NS-SLB) was prepared and further modified with a hyaluronic acid-cholesterol conjugate (NS-SLB-HC) to improve the CD44 targeting proficiency of NS-SLB. To validate the accumulation of CD44 and ensure minimal cytotoxicity, cellular uptake and cytotoxicity assessments were carried out for the nanosuspensions. Western blotting was employed to evaluate the anti-hepatic fibrosis efficacy in LX-2 cells by inhibiting the secretion of collagen I. Hepatic fibrosis mouse models were used to further confirm the effectiveness of NS-SLB and NS-SLB-HC against hepatic fibrosis in vivo. Results: Uniform nanosuspensions were prepared through self-assembly, achieving high drug loading rates of 89.44% and 60.67%, respectively. Both SLB nanosuspensions showed minimal cytotoxicity in cellular environments and mitigated hepatic fibrosis in vitro. NS-SLB-HC was demonstrated to target activated hepatic stellate cells by receptor-ligand interaction between HA and CD44. They can reverse hepatic fibrosis in vivo by downregulating TGF-β and inhibiting the secretion of α-SMA and collagen I. Conclusion: Designed as a medical excipient analogue, SLB-M was aimed to establish an innovative nanosuspension preparation method, characterized by high drug loading capacity and a notable impact against hepatic fibrosis.

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Proteomic Changes of Activated Hepatic Stellate Cells

Cited by 10 publications

References 58 publications

Huc-MSC-derived exosomes modified with the targeting peptide of aHSCs for liver fibrosis therapy

Huc-MSC-derived exosomes modified with the targeting peptide of aHSCs for liver fibrosis therapy

Extracellular vesicles targeting non-parenchymal cells: the therapeutical effect on liver fibrosis

Combined Amphiphilic Silybin Meglumine Nanosuspension Effective Against Hepatic Fibrosis in Mice Model

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