Isoliquiritigenin alleviates the development of alcoholic liver fibrosis by inhibiting ANXA2 - 03/02/23
, Shenghui Chu a, ⁎ Abstract |
The study aimed to investigate the effect of isoliquiritigenin (ISL) on model of alcoholic liver fibrosis (ALF). C57BL/6 mice were used to establish animal model of ALF, HSC-T6 cells were used to establish alcohol-activated cell model, and tandem mass tag (TMT) assays were used to analyze the proteome. The results showed that ISL obviously alleviated hepatic fibrosis in model mice. ISL visually improved the area of liver pathological stasis and deposition of fibrillar collagen (Sirius Red staining, Masson staining), inhibited the mRNA expression levels of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) in liver tissues. ISL down-regulated the mRNA expression levels of IL-6 and transforming growth factor-β1(TGF-β1) in activated hepatic stellate cells (HSCs). And ISL significantly reduced annexin A2 (ANXA2) in vitro detected by TMT proteomics technology. Interestingly, it was found for the first time that ISL could inhibit ANXA2 expression both in vivo and in vitro, block the sphingosine kinases (SPHKs)/sphingosine-1-phosphate (S1P)/interleukin 17 (IL-17) signaling pathway and regulate the expression of α-smooth muscle actin (α-SMA) by inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at the downstream signal to finally reverse HSCs activation and hepatic fibrosis. Thus, we demonstrated that ISL is a drug monomer with notable anti-hepatic fibrosis activity.
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Highlights |
• | ISL alleviated liver fibrosis in drinking mice and inhibited the activation of alcohol-stimulated hepatic stellate cells. |
• | TMT proteomics assay screening identified ANXA2, a key protein affecting hepatic stellate cell activation. |
• | ISL alleviated alcoholic liver fibrosis in mice by inhibiting ANXA2 expression, and blocking SPHKs/S1P/IL-17 signals. |
Abbreviations : AF, ALD, ALF, ALT, AST, aHSCs, BCA, CCL2, COL1A1, DMEM, DMSO, ECM, FBS, HSCs, MMP2, mRNA, PF, qRT-PCR, RIPA, S1P, S1PR1, SPHKs, STAT3, TIMP-1, α-SMA
Keywords : Alcoholic liver fibrosis, Hepatic stellate cells, Annexin A2, Isoliquiritigenin, SPHKs/S1P/Th17 signaling, Inflammation
Plan
Vol 159
Article 114173- mars 2023 Retour au numéro
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