S-adenosylmethionine inhibits the activated phenotype of human hepatic stellate cells via Rac1 and Matrix metalloproteinases |
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| Affiliation: | 1. Biotechnology Research Division, National Institute of Fisheries Science, 408-1 Sirang-ri, Gijang-up, Gijang-gun, Busan 46083, Republic of Korea;2. Department of Aquatic Life Medicine, College of Fisheries Science, Pukyong National University, 45, Yongso-ro, Nam-Gu, Busan, Republic of Korea;3. Department of Marine Biology & Aquaculture, College of Marine Science, Gyeongsang National University, 455, Tongyeong 650-160, Republic of Korea;1. Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan;2. Northwood High School, Irvine, CA, USA;3. Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung 40402, Taiwan;4. Department of Biotechnology, Asia University, Taiwan;1. JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, NIHR Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK;1. Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China;2. Department of Basic Theory of Mongolian medicine, Institute of Mongolian Medicine, Inner Mongolia Medical University, Hohhot 010110, China;1. Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA, USA;2. Department of Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;3. Department of Biological Sciences, University of South Carolina, Columbia, SC, USA |
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| Abstract: | ObjectiveTo investigate the effects of S-adenosylmethionine (SAM) on the proliferation, adhesion, migration, invasion and apoptosis of activated human hepatic stellate cells (HSCs) and to explore the relevant potential mechanisms.MethodsHuman HSCs LX-2 were cultured with SAM. The proliferation and adhesion were detected by CCK-8. Cell apoptosis rate were analyzed by flow cytometry, and cell migration and invasion were tested by the transwell assay. The expression of Rac1 and MMP-2 was identified by real-time PCR or Western blotting, and activated Rac1 was detected by GST pull-down assay. The activity of MMP-2 and MMP-9 was analyzed by substrate zymography.ResultsThe proliferation of LX-2 cells was inhibited by SAM, exhibiting a dose-dependent manner. Cell apoptosis rate induced by SAM was remarkably increased. SAM decreased the adhesion, migration and invasion of LX-2 cells. The expression and activation of Rac1 in LX-2 cells were significantly suppressed by SAM. In contrast, the activity of MMP-2 and MMP-9 was enhanced by SAM. SAM attenuated the up-regulated expression of Smad3/4 and Rac1 induced by TGF-β1.ConclusionSAM inhibits the proliferation, adhesion, migration and invasion of LX-2 cells in vitro probably via attenuating the expression and activation of Rac1 and up-regulating MMP-2 and MMP-9 expression, which possibly provide a molecular basis for potential application of SAM in the therapy of liver fibrosis. |
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