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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.
Acta Pharmacol Sin. 2019 Jul; 40(7):879-894.AP

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.

Authors+Show Affiliations

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.Jiangsu Key Laboratory of Targeted Antiviral Research, Chia Tai Tianqing Pharmaceutical Group Co., Ltd, Nanjing, 210023, China.Jiangsu Key Laboratory of Targeted Antiviral Research, Chia Tai Tianqing Pharmaceutical Group Co., Ltd, Nanjing, 210023, China.State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.Jiangsu Key Laboratory of Targeted Antiviral Research, Chia Tai Tianqing Pharmaceutical Group Co., Ltd, Nanjing, 210023, China. ghm@cttq.com.State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China. kongld@nju.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30568253

Citation

Yang, Yan-Zi, et al. "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." Acta Pharmacologica Sinica, vol. 40, no. 7, 2019, pp. 879-894.
Yang YZ, Zhao XJ, Xu HJ, et al. 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. Acta Pharmacol Sin. 2019;40(7):879-894.
Yang, Y. Z., Zhao, X. J., Xu, H. J., Wang, S. C., Pan, Y., Wang, S. J., Xu, Q., Jiao, R. Q., Gu, H. M., & Kong, L. D. (2019). 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. Acta Pharmacologica Sinica, 40(7), 879-894. https://doi.org/10.1038/s41401-018-0194-4
Yang YZ, et al. 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. Acta Pharmacol Sin. 2019;40(7):879-894. PubMed PMID: 30568253.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Yang,Yan-Zi, AU - Zhao,Xiao-Juan, AU - Xu,Hong-Jiang, AU - Wang,Shan-Chun, AU - Pan,Ying, AU - Wang,Shui-Juan, AU - Xu,Qiang, AU - Jiao,Rui-Qing, AU - Gu,Hong-Mei, AU - Kong,Ling-Dong, Y1 - 2018/12/19/ PY - 2018/05/30/received PY - 2018/11/08/accepted PY - 2018/12/21/pubmed PY - 2020/1/14/medline PY - 2018/12/21/entrez KW - EMT KW - JAK2/STAT3 pathway KW - MicroRNA-375-3p KW - TGF-β1/Smad signaling KW - excessive fructose intake KW - magnesium isoglycyrrhizinate SP - 879 EP - 894 JF - Acta pharmacologica Sinica JO - Acta Pharmacol Sin VL - 40 IS - 7 N2 - 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. SN - 1745-7254 UR - https://www.unboundmedicine.com/medline/citation/30568253/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_ L2 - https://doi.org/10.1038/s41401-018-0194-4 DB - PRIME DP - Unbound Medicine ER -