The role of ERK-RSK signaling in the proliferation of intrahepatic biliary epithelial cells exposed to microcystin-leucine arginine |
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| Affiliation: | 1. Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China;2. Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China;3. Department of Hepatopancreatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China;1. Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China;2. University of Chinese Academy of Sciences, Beijing, 100049, China;3. Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China;1. Department of Hepatopancreatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321, Nanjing, 210008, Jiangsu Province, China;2. Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China;3. Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China;4. State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China;5. Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Research Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden;1. Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China;2. Departments of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA;3. Department of Cellular, Molecular, and Biomedical Sciences, University of New Hampshire, Rudman Hall, 46 College Road, Durham, NH 03824, USA;1. Immunology and Reproduction Biology Laboratory, State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, 210093, China;2. Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, 210093, China;3. Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China;4. Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China |
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| Abstract: | Microcystin-leucine arginine (MC-LR) is a potent specific hepatotoxin produced by cyanobacteria in diverse water systems, and it has been documented to induce liver injury and hepatocarcinogenesis. However, its toxic effects on intrahepatic biliary epithelial cells have not been invested in detail. In this study, we aimed to investigate the effects of MC-LR exposure on the intrahepatic biliary epithelial cells in the liver. MC-LR was orally administered to mice at 1 μg/L, 7.5 μg/L, 15 μg/L, or 30 μg/L for 180 consecutive days for histopathological and immunoblot analysis. We observed that MC-LR can enter intrahepatic bile duct tissue and induce hyperplasia of mice. Human primary intrahepatic biliary epithelial cells (HiBECs) were cultured with various concentrations of MC-LR for 24 h, meanwhile the cell viability and proteins level were detected. Western blotting analysis revealed that MC-LR increased RSK phosphorylation via ERK signaling. RSK participated in cell proliferation and cell cycle progression. Taken together, after chronic exposure, MC-LR-treated mice exhibited abnormal bile duct hyperplasia and thickened bile duct morphology through activating the ERK-RSK signaling. These data support the potential toxic effects of MC-LR on bile duct tissue of the liver. |
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| Keywords: | MC-LR Intrahepatic biliary epithelial cells Proliferation ERK-RSK signaling |
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