2,3,5,4′-Tetrahydroxy-stilbene-2-<i>O</i>-beta-<scp>d</scp>-glucoside induces autophagy-mediated apoptosis in hepatocytes by upregulating miR-122 and inhibiting the PI3K/Akt/mTOR pathway: implications for its hepatotoxicity

Yang, Lei; Wu, Xing; Xiao, Wang-Zhong; Tang, Lin; Wang, Lu; Liu, Mengjiao; Dai, Bing

doi:10.1080/13880209.2020.1803367

Cited by 7 publications

(2 citation statements)

References 31 publications

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“…THSG treatment has been proven to induce autophagy by upregulation of autophagy-related proteins Beclin 1, LC3-II, and ATG12 in the liver tissues of prediabetic rats (Wang et al, 2020). It was also reported that THSG significantly induced autophagy and increased the expression of LC3-II protein in human WRL-68 hepatic cells (Yang et al, 2020). Consistent with those reports above, our results revealed that THSG treatment dramatically increased the protein levels of Beclin 1 and LC3B-II in TGF-β1stimulated MRC-5 human lung fibroblast cells.…”

Section: Discussionmentioning

confidence: 95%

“…Accumulating evidence has also shown that the repression of TGF-β1-induced activation of mTOR signaling in lung fibroblasts, which results in the induction of autophagy and the inhibition of myofibroblast activation and ECM production in mice model of BLM-induced pulmonary fibrosis ( Li et al, 2021 ; Lu et al, 2022 ). Furthermore, THSG has been demonstrated to trigger autophagy in human hepatocytes via the inhibition of the PI3K/Akt/mTOR signaling pathway ( Yang et al, 2020 ). Herein, these findings indicate that THSG inhibits the TGF-β1-induced Akt/mTOR pathway in human lung fibroblasts and alveolar epithelial cells, thereby leading to autophagy activation and subsequent alleviating lung fibrosis.…”

Section: Discussionmentioning

confidence: 99%

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2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside ameliorates bleomycin-induced pulmonary fibrosis via regulating pro-fibrotic signaling pathways

Huang

Chen

et al. 2022

Front. Pharmacol.

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2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-Glucoside (THSG) is the main active ingredient extracted from Polygonum multiflorum Thunb. (PMT), which has been reported to possess extensive pharmacological properties. Nevertheless, the exact role of THSG in pulmonary fibrosis has not been demonstrated yet. The main purpose of this study was to investigate the protective effect of THSG against bleomycin (BLM)-induced lung fibrosis in a murine model, and explore the underlying mechanisms of THSG in transforming growth factor-beta 1 (TGF-β1)-induced fibrogenesis using MRC-5 human lung fibroblast cells. We found that THSG significantly attenuated lung injury by reducing fibrosis and extracellular matrix deposition. THSG treatment significantly downregulated the expression levels of TGF-β1, fibronectin, α-SMA, CTGF, and TGFBR2, however, upregulated the expression levels of antioxidants (SOD-1 and catalase) and LC3B in the lungs of BLM-treated mice. THSG treatment decreased the expression levels of fibronectin, α-SMA, and CTGF in TGF-β1-stimulated MRC-5 cells. Conversely, THSG increased the expression levels of SOD-1 and catalase. Furthermore, treatment of THSG profoundly reduced the TGF-β1-induced generation of reactive oxygen species (ROS). In addition, THSG restored TGF-β1-induced impaired autophagy, accompany by increasing the protein levels of LC3B-II and Beclin 1. Mechanism study indicated that THSG significantly reduced TGF-β1-induced increase of TGFBR2 expression and phosphorylation of Smad2/3, Akt, mTOR, and ERK1/2 in MRC-5 cells. These findings suggest that THSG may be considered as an anti-fibrotic drug for the treatment of pulmonary fibrosis.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside ameliorates bleomycin-induced pulmonary fibrosis via regulating pro-fibrotic signaling pathways

Huang

Chen

et al. 2022

Front. Pharmacol.

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Silencing of IGF2BP1 restrains ox‐LDL‐induced lipid accumulation and inflammation by reducing RUNX1 expression and promoting autophagy in macrophages

Liu

Gao

Cao

et al. 2022

J Biochem & Molecular Tox

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Atherosclerosis (AS) is a chronic inflammatory disease with the formation and accumulation of macrophage‐derived foam cells in the subendothelial space of blood vessels as one major characteristic. Insulin‐like growth factor 2 messenger RNA (mRNA) binding protein 1 (IGF2BP1) is an RNA‐binding factor and its elevation has been reported to be associated with macrophage infiltration into the atherosclerotic vascular wall. This study aims to investigate the roles of IGF2BP1 in AS‐associated foam cell formation. Herein, ApoE−/− mice fed with high‐fat diet developed atherosclerotic lesions in the aorta, where IGF2BP1 expression was upregulated and autophagy was impaired. IGF2BP1 expressed in F4/80+ macrophages and coexisted with p62. In vitro, IGF2BP1 expression was upregulated in RAW264.7 macrophages exposed to oxidized low‐density lipoprotein (ox‐LDL) (100 μg/ml). Interestingly, silencing of IGF2BP1 ameliorated ox‐LDL‐induced lipid accumulation and inflammation, and enhanced autophagic flux in macrophages. Furthermore, the expression of RUNX family transcription factor 1 (RUNX1), a gene that is able to inhibit autophagy in multiple cell types, was elevated in atherosclerotic aortas and in ox‐LDL‐treated macrophages. In addition, RNA immunoprecipitation results revealed that IGF2BP1 is bound to RUNX1 mRNA. Alterations induced by IGF2BP1 knockdown in ox‐LDL‐treated macrophages were abolished by RUNX1 overexpression. Furthermore, after autophagy inhibitor 3‐methyladenine administration, silencing of IGF2BP1‐reduced lipid accumulation and inflammation were recovered in RAW264.7 cells. In summary, our study demonstrated that silencing of IGF2BP1 restrained ox‐LDL‐induced lipid accumulation and inflammation by reducing RUNX1 expression and facilitating autophagy in macrophages. IGF2BP1/RUNX1 axis may be considered as a potential therapeutic target in AS.

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Real-time screening of hepatotoxins in natural medicine by peroxynitrite responsive lanthanide-based NIR-II luminescent probes

et al. 2022

Chemical Engineering Journal

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2,3,5,4′-Tetrahydroxy-stilbene-2-O-beta-d-glucoside induces autophagy-mediated apoptosis in hepatocytes by upregulating miR-122 and inhibiting the PI3K/Akt/mTOR pathway: implications for its hepatotoxicity

Abstract: Dai (2020) 2,3,5,4′-Tetrahydroxy-stilbene-2-O-beta-d-glucoside induces autophagymediated apoptosis in hepatocytes by upregulating miR-122 and inhibiting the PI3K/Akt/mTOR pathway: implications for its hepatotoxicity,

Cited by 7 publications

References 31 publications

2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside ameliorates bleomycin-induced pulmonary fibrosis via regulating pro-fibrotic signaling pathways

2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside ameliorates bleomycin-induced pulmonary fibrosis via regulating pro-fibrotic signaling pathways

Silencing of IGF2BP1 restrains ox‐LDL‐induced lipid accumulation and inflammation by reducing RUNX1 expression and promoting autophagy in macrophages

Real-time screening of hepatotoxins in natural medicine by peroxynitrite responsive lanthanide-based NIR-II luminescent probes

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