1. Magnesium isoglycyrrhizinate ameliorates high fructose-induced liver fibrosis in rat by increasing miR-375-3p to suppress JAK2/STAT3 pathway and TGF-β1/Smad signaling
- Author
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Hong-Jiang Xu, Xiao-juan Zhao, Shui-Juan Wang, Shan-Chun Wang, Rui-qing Jiao, Pan Ying, Ling-Dong Kong, Hong-Mei Gu, Qiang Xu, and Yan-Zi Yang
- Subjects
0301 basic medicine ,Pharmacology ,biology ,Kinase ,Chemistry ,Cell ,General Medicine ,SMAD ,Transfection ,Article ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Mir-375 ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,STAT protein ,medicine ,Pharmacology (medical) ,STAT3 ,Transforming growth factor - Abstract
Increasing evidence has demonstrated that excessive fructose intake induces liver fibrosis. Epithelial–mesenchymal transition (EMT) driven by transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog (Smad) signaling activation promotes the occurrence and development of liver fibrosis. Magnesium isoglycyrrhizinate is clinically used as a hepatoprotective agent to treat liver fibrosis, but its underlying molecular mechanism has not been identified. Using a rat model, we found that high fructose intake reduced microRNA (miR)-375-3p expression and activated the janus-activating kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) cascade and TGF-β1/Smad signaling, which is consistent with the EMT and liver fibrosis. To further verify these observations, BRL-3A cells and/or primary rat hepatocytes were exposed to high fructose and/or transfected with a miR-375-3p mimic or inhibitor or treated with a JAK2 inhibitor, and we found that the low expression of miR-375-3p could induce the JAK2/STAT3 pathway to activate TGF-β1/Smad signaling and promote the EMT. Magnesium isoglycyrrhizinate was found to ameliorate high fructose-induced EMT and liver fibrosis in rats. More importantly, magnesium isoglycyrrhizinate increased miR-375-3p expression to suppress the JAK2/STAT3 pathway and TGF-β1/Smad signaling in these animal and cell models. This study provides evidence showing that magnesium isoglycyrrhizinate attenuates liver fibrosis associated with a high fructose diet.
- Published
- 2018