Hepatic stellate cells specific liposomes with the Toll‐like receptor 4 shRNA attenuates liver fibrosis

Zhang, Yuwei; Li, Yang; Mu, Tong; Tong, Nanwei; Cheng, Ping

doi:10.1111/jcmm.16209

Cited by 10 publications

(4 citation statements)

References 53 publications

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“…Excessive ROS produced by diverse oxidative biochemical enzymes disturbs the normal action of liver-specific cells and probably engages in liver fibrosis occurrence. [44] Moreover, ROS generation is implicated in HSC activation, [45,46] revealing its importance in liver fibrosis. We found that ROS level was elevated in TGF-β1-induced LX-2 cells, whereas reduced after Tβ4 overexpression.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of thymosin β4 in ameliorating liver fibrosis via the MAPK/NF‐κB pathway

Wang

Zhang

Wang³

et al. 2023

J Biochem & Molecular Tox

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Liver fibrosis is a grievous global challenge, where hepatic stellate cells (HSCs) activation is a paramount step. This study analyzed the mechanism of Tβ4 in ameliorating liver fibrosis via the MAPK/NF-κB pathway. The liver fibrosis mouse models were established via bile duct ligation (BDL) and verified by HE and Masson staining. TGF-β1-induced activated LX-2 cells were employed in vitro experiments. Tβ4 expression was determined using RT-qPCR, HSC activation markers were examined using Western blot analysis, and ROS levels were tested via DCFH-DA kits. Cell proliferation, cycle, and migration were examined by CCK-8, flow cytometry, and Transwell assays, respectively. Effects of Tβ4 on liver fibrosis, HSC activation, ROS production, and HSC growth were analyzed after transfection of constructed Tβ4-overexpressing lentiviral vectors. MAPK/NF-κB-related protein levels were tested using Western blotting and p65 expression in the nucleus was detected through immunofluorescence. Regulation of MAPK/NF-κB pathway in TGF-β1-induced LX-2 cells was explored by adding MAPK activator U-46619 or inhibitor SB203580. Furthermore, its regulating in liver fibrosis was verified by treating BDL mice overexpressing Tβ4 with MAPK inhibitor or activator. Tβ4 was downregulated in BDL mice. Tβ4 overexpression inhibited liver fibrosis. In TGF-β1induced fibrotic LX-2 cells, Tβ4 was reduced and cell migration and proliferation were enhanced with elevated ROS levels, while Tβ4 overexpression suppressed cell migration and proliferation. Tβ4 overexpression blocked the MAPK/NF-κB pathway activation by reducing ROS production, thus inhibiting liver fibrosis in TGF-β1 induced LX-2 cells and BDL mice. Tβ4 ameliorates liver fibrosis by impeding the MAPK/NF-κB pathway activation.

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Section: Discussionmentioning

confidence: 99%

Mechanism of thymosin β4 in ameliorating liver fibrosis via the MAPK/NF‐κB pathway

Wang

Zhang

Wang³

et al. 2023

J Biochem & Molecular Tox

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“…Recent developments in terms of delivery of RA and RAR-selective retinoids include delivery in nanoparticles (149)(150)(151) and delivery in liposomes (152,153). Interestingly, the properties of VA itself have been used to enhance specific delivery of cationic liposomes containing short hairpin RNAs to stellate cells in the liver (154). An excellent review on the formulation and delivery of retinoids was recently published (155).…”

Section: Challenges Of Developing Synthetic Retinoids Into Drugsmentioning

confidence: 99%

Synthetic Retinoids Beyond Cancer Therapy

Gudas

2022

Annu. Rev. Pharmacol. Toxicol.

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While the uses of retinoids for cancer treatment continue to evolve, this review focuses on other therapeutic areas in which retinoids [retinol (vitamin A), all- trans retinoic acid (RA), and synthetic retinoic acid receptor (RAR)α-, β-, and γ-selective agonists] are being used and on promising new research that suggests additional uses for retinoids for the treatment of disorders of the kidneys, skeletal muscles, heart, pancreas, liver, nervous system, skin, and other organs. The most mature area, in terms of US Food and Drug Administration–approved, RAR-selective agonists, is for treatment of various skin diseases. Synthetic retinoid agonists have major advantages over endogenous RAR agonists such as RA. Because they act through a specific RAR, side effects may be minimized, and synthetic retinoids often have better pharmaceutical properties than does RA. Based on our increasing knowledge of the multiple roles of retinoids in development, epigenetic regulation, and tissue repair, other exciting therapeutic areas are emerging. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…Fully activated HSCs release and upregulate expression of TIMP-1 and TIMP-2, which inactivate MMPs through proteolytic cleavage [ 43 , 45 , 48 ]. Targeting activated HSCs in vivo decreased the expression of TIMP-1 and TIMP-2 and resulted in attenuated liver fibrosis [ 49 ]. Impairment of HSCs activation in mice downregulated TIMP-1 and diminished alcohol-induced steatohepatitis [ 50 ].…”

Section: The Role Of Ahscs In Hccmentioning

confidence: 99%

Activated Hepatic Stellate Cells in Hepatocellular Carcinoma: Their Role as a Potential Target for Future Therapies

Ali

Trailin

Ambrożkiewicz

et al. 2022

IJMS

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Hepatocellular carcinoma (HCC) is a global healthcare challenge, which affects more than 815,000 new cases every year. Activated hepatic stellate cells (aHSCs) remain the principal cells that drive HCC onset and growth. aHSCs suppress the anti-tumor immune response through interaction with different immune cells. They also increase the deposition of the extracellular matrix proteins, challenging the reversion of fibrosis and increasing HCC growth and metastasis. Therapy for HCC was reported to activate HSCs, which could explain the low efficacy of current treatments. Conversely, recent studies aimed at the deactivation of HSCs show that they have been able to inhibit HCC growth. In this review article, we discuss the role of aHSCs in HCC pathophysiology and therapy. Finally, we provide suggestions for the experimental implementation of HSCs in HCC therapies.

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Hepatic stellate cells specific liposomes with the Toll‐like receptor 4 shRNA attenuates liver fibrosis

Cited by 10 publications

References 53 publications

Mechanism of thymosin β4 in ameliorating liver fibrosis via the MAPK/NF‐κB pathway

Mechanism of thymosin β4 in ameliorating liver fibrosis via the MAPK/NF‐κB pathway

Synthetic Retinoids Beyond Cancer Therapy

Activated Hepatic Stellate Cells in Hepatocellular Carcinoma: Their Role as a Potential Target for Future Therapies

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