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Penta-acetyl Geniposide Suppresses Migration, Invasion, and Inflammation of TNF-α-Stimulated Rheumatoid Arthritis Fibroblast-Like Synoviocytes Involving Wnt/β-Catenin Signaling Pathway.

التفاصيل البيبلوغرافية
العنوان: Penta-acetyl Geniposide Suppresses Migration, Invasion, and Inflammation of TNF-α-Stimulated Rheumatoid Arthritis Fibroblast-Like Synoviocytes Involving Wnt/β-Catenin Signaling Pathway.
المؤلفون: Cai L; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, People's Republic of China.; Department of Pathology, School of Basic Medicine, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, People's Republic of China., Mu YR; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, People's Republic of China., Liu MM; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, People's Republic of China., Zhou MY; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, People's Republic of China., Meng B; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, People's Republic of China., Liu FY; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, People's Republic of China., Li R; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, People's Republic of China. aydlirong@163.com.
المصدر: Inflammation [Inflammation] 2021 Dec; Vol. 44 (6), pp. 2232-2245. Date of Electronic Publication: 2021 Jun 08.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Kluwer Academic/Plenum Publishers Country of Publication: United States NLM ID: 7600105 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-2576 (Electronic) Linking ISSN: 03603997 NLM ISO Abbreviation: Inflammation Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : New York, NY : Kluwer Academic/Plenum Publishers
Original Publication: New York, Plenum Press.
مواضيع طبية MeSH: Anti-Inflammatory Agents/*pharmacology , Antirheumatic Agents/*pharmacology , Arthritis, Experimental/*prevention & control , Arthritis, Rheumatoid/*prevention & control , Cell Movement/*drug effects , Fibroblasts/*drug effects , Iridoid Glucosides/*pharmacology , Synoviocytes/*drug effects , Wnt Signaling Pathway/*drug effects, Animals ; Arthritis, Experimental/immunology ; Arthritis, Experimental/metabolism ; Arthritis, Experimental/pathology ; Arthritis, Rheumatoid/immunology ; Arthritis, Rheumatoid/metabolism ; Arthritis, Rheumatoid/pathology ; Cell Line ; Fibroblasts/immunology ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Humans ; Inflammation Mediators/metabolism ; Male ; Matrix Metalloproteinases/metabolism ; Rats, Sprague-Dawley ; Synoviocytes/immunology ; Synoviocytes/metabolism ; Synoviocytes/pathology ; Tumor Necrosis Factor-alpha/toxicity ; Rats
مستخلص: We previously reported that penta-acetyl geniposide ((Ac) 5 GP, an active derivative of geniposide) showed anti-arthritic effect on adjuvant-induced arthritis (AIA) rats by promoting the apoptosis of AIA fibroblast-like synoviocyte (FLS). This study aimed to demonstrate the effects of (Ac) 5 GP on migration, invasion, and inflammation of TNF-α-stimulated rheumatoid arthritis (RA) FLS (MH7A cell) and to explore the involved mechanisms. MTT assay was used to determine the applied non-cytotoxic doses of (Ac) 5 GP (12.5, 25, 50 μM) in vitro. Results of wound-healing, transwell, and phalloidin staining assays indicated that (Ac) 5 GP reduced the migration, invasion, and F-actin cytoskeletal reorganization of TNF-α-stimulated MH7A. Results of ELISA and western blot assays confirmed that (Ac) 5 GP reduced TNF-α-induced production of pro-inflammatory cytokines (like IL-1β, IL-6, IL-8) and matrix metalloproteinases (MMPs, such as MMP-2 and MMP-9). Moreover, (Ac) 5 GP inhibited TNF-α-induced activation of Wnt/β-catenin pathway, evidenced by reducing the protein levels of Wnt1, p-GSK-3β (Ser9), and β-catenin and preventing β-catenin nuclear translocation. Importantly, the combination of XAV939 (an inhibitor of Wnt/β-catenin) promoted the actions of (Ac) 5 GP on TNF-α-induced migration, invasion, and inflammation, further revealing the involvement of Wnt/β-catenin pathway underlying the therapeutic effects of (Ac) 5 GP on TNF-α-stimulated MH7A. In vivo, (Ac) 5 GP relieved the progression and severity of rat collagen-induced arthritis, related to reducing the levels of IL-1β, IL-6, IL-8, MMP-2, and MMP-9 as well as inhibiting Wnt/β-catenin pathway in synovial tissues. Collectively, (Ac) 5 GP could suppress TNF-α-induced migration, invasion, and inflammation in RA FLS involving Wnt/β-catenin pathway and (Ac) 5 GP might be as a candidate agent for RA treatment.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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معلومات مُعتمدة: 81972040 National Natural Science Foundation of China; 81102273 National Natural Science Foundation of China; gxyqZD2016045 Program for Outstanding Young Talents of Higher Education Institution of Anhui Province; IMMDL202001 Open Project Program of Inflammation and Immune Mediated Diseases Laboratory of Anhui Province
فهرسة مساهمة: Keywords: Wnt/β-catenin signaling pathway; fibroblast-like synoviocyte; inflammation; migration; penta-acetyl geniposide; rheumatoid arthritis
المشرفين على المادة: 0 (Anti-Inflammatory Agents)
0 (Antirheumatic Agents)
0 (Inflammation Mediators)
0 (Iridoid Glucosides)
0 (Tumor Necrosis Factor-alpha)
49776-64-9 (pentaacetyl geniposide)
EC 3.4.24.- (Matrix Metalloproteinases)
تواريخ الأحداث: Date Created: 20210608 Date Completed: 20220317 Latest Revision: 20240226
رمز التحديث: 20240226
DOI: 10.1007/s10753-021-01495-y
PMID: 34101073
قاعدة البيانات: MEDLINE
الوصف
تدمد:1573-2576
DOI:10.1007/s10753-021-01495-y