Glycogen Metabolism and Rheumatoid Arthritis: The Role of Glycogen Synthase 1 in Regulation of Synovial Inflammation via Blocking AMP-Activated Protein Kinase Activation
| العنوان: | Glycogen Metabolism and Rheumatoid Arthritis: The Role of Glycogen Synthase 1 in Regulation of Synovial Inflammation via Blocking AMP-Activated Protein Kinase Activation |
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| المؤلفون: | Maohua Shi, Jingnan Wang, Youjun Xiao, Cuicui Wang, Qian Qiu, Minxi Lao, Yangtao Yu, Zhifeng Li, Hongwei Zhang, Yujin Ye, Liuqin Liang, Xiuyan Yang, Guoqiang Chen, Hanshi Xu |
| المصدر: | Frontiers in Immunology Frontiers in Immunology, Vol 9 (2018) |
| بيانات النشر: | Frontiers Media S.A., 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Fibroblast-like synoviocyte, rheumatoid arthritis, Inflammatory arthritis, Gene Expression, Arthritis, AMP-Activated Protein Kinases, Arthritis, Rheumatoid, chemistry.chemical_compound, 0302 clinical medicine, AMP-activated protein kinase, Cell Movement, Immunology and Allergy, Original Research, biology, Glycogen, Chemistry, Synovial Membrane, Middle Aged, Immunohistochemistry, Synoviocytes, Glycogen Synthase, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, glycogen, Carbohydrate Metabolism, Cytokines, Female, Inflammation Mediators, lcsh:Immunologic diseases. Allergy, Adult, medicine.medical_specialty, Immunology, 03 medical and health sciences, Internal medicine, medicine, Humans, glycogen synthase 1, Protein kinase A, Glycogen synthase, Aged, Cell Proliferation, AMPK, Ribonucleotides, Aminoimidazole Carboxamide, Hypoxia-Inducible Factor 1, alpha Subunit, medicine.disease, 030104 developmental biology, Endocrinology, inflammation, biology.protein, activation, fibroblast-like synoviocyte, lcsh:RC581-607, Biomarkers |
| الوصف: | Objective To investigate the role of glycogen metabolism in regulating rheumatoid fibroblast-like synoviocyte (FLS)-mediated synovial inflammation and its underlying mechanism. Methods FLSs were separated from synovial tissues (STs) obtained from rheumatoid arthritis (RA) patients. Glycogen content was determined by periodic acid Schiff staining. Protein expression was analyzed by Western blot or immunohistochemistry. Gene expression of cytokines and matrix metalloproteinases (MMPs) was evaluated by quantitative real-time PCR. FLS proliferation was detected by EdU incorporation. Migration and invasion were measured by Boyden chamber assay. Results Glycogen levels and glycogen synthase 1 (GYS1) expression were significantly increased in the ST and FLSs of RA patients. TNF-α or hypoxia induced GYS1 expression and glycogen synthesis in RA FLSs. GYS1 knockdown by shRNA decreased the expression of IL-1β, IL-6, CCL-2, MMP-1, and MMP-9 and proliferation and migration by increasing AMP-activated protein kinase (AMPK) activity in RA FLS. AMPK inhibitor or knockdown AMPK could reverse the inhibitory effect of GYS1 knockdown on the inflammatory response in RA FLSs; however, an AMPK agonist blocked RA FLS activity. We further determined that hypoxia-inducible factor-1α mediates TNF-α- or hypoxia-induced GYS1 expression and glycogen levels. Local joint depletion of GYS1 or intraperitoneal administration with an AMPK agonist ameliorated the severity of arthritis in rats with collagen-induced arthritis. Conclusion Our data demonstrate that GYS1-mediated glycogen accumulation contributes to FLS-mediated synovial inflammation in RA by blocking AMPK activation. In our knowledge, this is a first study linking glycogen metabolism to chronic inflammation. Inhibition of GYS1 might be a novel therapeutic strategy for chronic inflammatory arthritis, including RA. |
| اللغة: | English |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::44ccf142a76a6f489574050f2a28aa0dTest http://europepmc.org/articles/PMC6072843Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....44ccf142a76a6f489574050f2a28aa0d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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