Abstract Title:

Pterostilbene prevents hepatocyte EMT in fructose-induced liver fibrosis through suppressing miR-34a/Sirt1/p53 and TGF-β1/Smads signaling.

Abstract Source:

Br J Pharmacol. 2019 Jan 10. Epub 2019 Jan 10. PMID: 30632134

Abstract Author(s):

Lin Song, Tian-Yu Chen, Xiao-Juan Zhao, Qiang Xu, Rui-Qing Jiao, Jian-Mei Li, Ling-Dong Kong

Article Affiliation:

Lin Song


BACKGROUND AND PURPOSE: Excessive fructose consumption is a risk factor liver fibrosis. Pterostilbene shows anti-liver fibrosis activity. Here, we investigated the potential role and the mechanisms underlying hepatocyte epithelial-mesenchymal transition (EMT) in fructose-induced liver fibrosis, as well as the protection of pterostilbene.

EXPERIMENTAL APPROACH: The characteristics of liver fibrosis in 10% fructose-fed rats and EMT in 5 mM fructose-exposed BRL-3A cells with or without pterostilbene, as well as the change of miR-34a/Sirt1/p53 and transforming growth factorβ1 (TGF-β1)/Smads signaling, were examined. MiR-34a inhibitor, miR-34a minic or p53 siRNA were used to explore the role of miR-34a/Sirt1/p53 signaling in fructose-induced EMT and the action of pterostilbene.

KEY RESULTS: Pterostilbene prevented fructose-induced liver injury with fibrosis in rats. Fructose caused hepatocyte undergoing EMT, gaining fibroblast-specific protein 1 (FSP1) and vimentin, and losing E-cadherin, attenuated by pterostilbene. Moreover, fructose induced miR-34a overexpression in hepatocytes with down-regulated Sirt1, increased p53 and ac-p53, and activated TGF-β1/Smads signaling, whereas these disturbances were suppressed by miR-34a inhibitor. Additionally, miR-34a inhibitor and p53 siRNA prevented TGF-β1-driven hepatocyte EMT under fructose exposure. Pterostilbene down-regulated miR-34a, up-regulated Sirt1 and suppressed p53 activation and TGF-β1/Smads signaling in fructose-induced animals and cells, but showed no superimposed effect with miR-34a inhibitor on miR-34a/Sirt1/p53 signaling in fructose-exposed hepatocytes.

CONCLUSIONS AND IMPLICATIONS: These results strongly support that the activation of miR-34a/Sirt1/p53 signaling is required for fructose-induced hepatocyte EMT mediated by TGF-β1/Smads signaling, contributing to liver fibrosis in rats. Pterostilbene exhibits a protective effect against liver fibrosis at least partly through inhibiting miR-34a/Sirt1/p53 signaling activation.

Study Type : Animal Study

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Sayer Ji
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