- Diabetes, obesity and metabolism
- Phloretin Ameliorates Succinate-Induced Liver Fibrosis by Regulating Hepatic Stellate Cells
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Cong Thuc Le, Giang Nguyen, So Young Park, Hanh Nguyen Dong, Yun Kyung Cho, Jae-Ho Lee, Seung-Soon Im, Dae-Hee Choi, Eun-Hee Cho
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Endocrinol Metab. 2023;38(4):395-405. Published online August 3, 2023
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DOI: https://doi.org/10.3803/EnM.2023.1661
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Abstract
PDFPubReader ePub
- Background
Hepatic stellate cells (HSCs) are the major cells which play a pivotal role in liver fibrosis. During injury, extracellular stimulators can induce HSCs transdifferentiated into active form. Phloretin showed its ability to protect the liver from injury, so in this research we would like to investigate the effect of phloretin on succinate-induced HSCs activation in vitro and liver fibrosis in vivo study.
Methods In in vitro, succinate was used to induce HSCs activation, and then the effect of phloretin on activated HSCs was examined. In in vivo, succinate was used to generated liver fibrosis in mouse and phloretin co-treated to check its protection on the liver.
Results Phloretin can reduce the increase of fibrogenic markers and inhibits the proliferation, migration, and contraction caused by succinate in in vitro experiments. Moreover, an upregulation of proteins associated with aerobic glycolysis occurred during the activation of HSCs, which was attenuated by phloretin treatment. In in vivo experiments, intraperitoneal injection of phloretin decreased expression of fibrotic and glycolytic markers in the livers of mice with sodium succinate diet-induced liver fibrosis. These results suggest that aerobic glycolysis plays critical role in activation of HSCs and succinate can induce liver fibrosis in mice, whereas phloretin has therapeutic potential for treating hepatic fibrosis.
Conclusion Intraperitoneal injection of phloretin attenuated succinate-induced hepatic fibrosis and alleviates the succinate-induced HSCs activation.
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Citations
Citations to this article as recorded by
- The potential of flavonoids in hepatic fibrosis: A comprehensive review
Zhu Wenbo, Han Jianwei, Liu Hua, Tang Lei, Chen Guijuan, Tian Mengfei Phytomedicine.2024; 133: 155932. CrossRef - Advancements in Plant-Based Therapeutics for Hepatic Fibrosis: Molecular Mechanisms and Nanoparticulate Drug Delivery Systems
Alina Ciceu, Ferenc Fenyvesi, Anca Hermenean, Simona Ardelean, Simona Dumitra, Monica Puticiu International Journal of Molecular Sciences.2024; 25(17): 9346. CrossRef
- Endocrine Research
- Irisin Regulates the Functions of Hepatic Stellate Cells
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Hanh Nguyen Dong, So Young Park, Cong Thuc Le, Dae-Hee Choi, Eun-Hee Cho
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Endocrinol Metab. 2020;35(3):647-655. Published online September 22, 2020
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DOI: https://doi.org/10.3803/EnM.2020.658
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7,158
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Abstract
PDFPubReader ePub
- Background
Hepatic stellate cells (HSCs) are known to play a fundamental role in the progression of liver fibrosis. Once HSCs are activated, they are involved in proliferation, migration, and contractility which are characteristics of liver fibrogenesis. Recent studies have shown that irisin, a myokine secreted during physical exercise, has a protective effect in various metabolic diseases, especially in renal fibrosis. However, whether irisin is involved in HSC activation and other processes associated with liver fibrosis has not yet been investigated. In this study, we reveal the role of irisin in HSC activation as well as in proliferation, migration, and contractile properties of HSCs in vitro.
Methods LX-2 cells, immortalized human HSCs, were treated with transforming growth factor beta 1 (TGF-β1), a core regulator of HSC fibrosis, with or without irisin, and markers of the aforementioned processes were analyzed. Further, an inflammatory response was stimulated with TGF-β1 and lipopolysaccharide (LPS) in combination with irisin and the expression of cytokines was measured.
Results Recombinant irisin significantly suppressed the expression of TGF-β1-stimulated fibrosis markers including alpha-smooth muscle actin and collagen type 1 alpha 1 and prevented the TGF-β1-induced proliferation, migration, and contractility of LX-2 cells. Additionally, irisin ameliorated the production of interleukin-6 (IL-6) and IL-1β induced by TGF-β1 and LPS treatments.
Conclusion These findings suggested that irisin potently improved the progression of hepatic fibrosis by regulating HSC activation, proliferation, migration, contractility, and HSC-mediated production of inflammatory cytokine.
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Citations
Citations to this article as recorded by
- Potential role of irisin in digestive system diseases
Yueming Zhang, Linxian Zhao, Huan Gao, Jinghui Zhai, Yanqing Song Biomedicine & Pharmacotherapy.2023; 166: 115347. CrossRef - Potential role of irisin in lung diseases and advances in research
Hongna Dong, Xuejiao Lv, Peng Gao, Yuqiu Hao Frontiers in Pharmacology.2023;[Epub] CrossRef - Stem bark ofFraxinus rhynchophyllaameliorates the severity of pancreatic fibrosis by regulating the TGF-β/Smad signaling pathway
Ji-Won Choi, Joon Yeon Shin, Ziqi Zhou, Dong-Uk Kim, Bitna Kweon, Hyuncheol Oh, Youn-Chul Kim, Ho-Joon Song, Gi-Sang Bae, Sung-Joo Park Journal of Investigative Medicine.2022; 70(5): 1285. CrossRef - Circadian rhythms and cancers: the intrinsic links and therapeutic potentials
Li Zhou, Zhe Zhang, Edouard Nice, Canhua Huang, Wei Zhang, Yong Tang Journal of Hematology & Oncology.2022;[Epub] CrossRef - Kinsenoside alleviates inflammation and fibrosis in experimental NASH mice by suppressing the NF-κB/NLRP3 signaling pathway
Yan-fang Deng, Qian-qian Xu, Tian-qi Chen, Jia-xiong Ming, Ya-fen Wang, Li-na Mao, Jia-jun Zhou, Wei-guang Sun, Qun Zhou, Hong Ren, Yong-hui Zhang Phytomedicine.2022; 104: 154241. CrossRef - The potential role of FNDC5/irisin in various liver diseases: awakening the sleeping beauties
Xiaoyu Wang, Lihong Mao, Chaoqun Li, Yangyang Hui, Zihan Yu, Mingyu Sun, Yifan Li, Gaoyue Guo, Wanting Yang, Binxin Cui, Xiaofei Fan, Chao Sun Expert Reviews in Molecular Medicine.2022;[Epub] CrossRef - The Effects of Irisin on the Interaction between Hepatic Stellate Cell and Macrophage in Liver Fibrosis
Dinh Vinh Do, So Young Park, Giang Thi Nguyen, Dae Hee Choi, Eun-Hee Cho Endocrinology and Metabolism.2022; 37(4): 620. CrossRef - Hepatic Steatosis Contributes to the Development of Muscle Atrophy via Inter-Organ Crosstalk
Kenneth Pasmans, Michiel E. Adriaens, Peter Olinga, Ramon Langen, Sander S. Rensen, Frank G. Schaap, Steven W. M. Olde Damink, Florian Caiment, Luc J. C. van Loon, Ellen E. Blaak, Ruth C. R. Meex Frontiers in Endocrinology.2021;[Epub] CrossRef - Physiopathology of Lifestyle Interventions in Non-Alcoholic Fatty Liver Disease (NAFLD)
David Carneros, Guillermo López-Lluch, Matilde Bustos Nutrients.2020; 12(11): 3472. CrossRef
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