Dasatinib ameliorates thioacetamide-induced liver fibrosis: modulation of miR-378 and miR-17 and their linked Wnt/β-catenin and TGF-β/smads pathways

被引：21
作者：
Zaafan, Mai A. [1 ]
Abdelhamid, Amr M. [2 ]
机构：
[1] October Univ Modern Sci & Arts MSA, Fac Pharm, Pharmacol & Toxicol Dept, Dokki, Egypt
[2] October Univ Modern Sci & Arts MSA, Fac Pharm, Biochem Dept, Dokki, Egypt
来源：
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2022年 / 37卷 / 01期
关键词：
Dasatinib; liver fibrosis; smad-3; Wnt-10; mice; HEPATIC STELLATE CELLS; BETA; ACTIVATION;
D O I：
10.1080/14756366.2021.1995379
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Hepatic stellate cells activation (HSCs) plays a crucial role in the pathogenesis of liver fibrosis. Specific microRNAs have been suggested to affect the activation of HSCs via various signalling pathways including TGF-beta/smads and Wnt/beta-catenin pathways. Dasatinib is a multitarget inhibitor of many tyrosine kinases has recently studied for its anti-fibrotic effects in a variety of fibrous diseases. This study investigated the role of modulation of miRNA-378 and miRNA-17 in the pathogenesis of liver fibrosis through altering Wnt/beta-catenin and TGF-beta/smads pathways and evaluated the beneficial effect of the tyrosine kinase inhibitor, dasatinib, in thioacetamide-induced liver fibrosis model in mice. Treatment with dasatinib down-regulated miRNA-17 expression, leading to the restoration of WiF-1 and smad-7 which cause the inhibition of both Wnt/beta-catenin and TGF-beta/smads signalling. In addition, it upregulated miRNA-378 leading to the decrease of Wnt-10 which contributes to the suppression of activated HSCs.
引用
收藏
页码：118 / 124
页数：7
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