Penta-acetyl Geniposide Suppresses Migration, Invasion, and Inflammation of TNF-α-Stimulated Rheumatoid Arthritis Fibroblast-Like Synoviocytes Involving Wnt/ß-Catenin Signaling Pathway.
Inflammation
; 44(6): 2232-2245, 2021 Dec.
Article
en En
| MEDLINE
| ID: mdl-34101073
ABSTRACT
We previously reported that penta-acetyl geniposide ((Ac)5GP, 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)5GP 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)5GP (12.5, 25, 50 µM) in vitro. Results of wound-healing, transwell, and phalloidin staining assays indicated that (Ac)5GP reduced the migration, invasion, and F-actin cytoskeletal reorganization of TNF-α-stimulated MH7A. Results of ELISA and western blot assays confirmed that (Ac)5GP reduced TNF-α-induced production of pro-inflammatory cytokines (like IL-1ß, IL-6, IL-8) and matrix metalloproteinases (MMPs, such as MMP-2 and MMP-9). Moreover, (Ac)5GP inhibited TNF-α-induced activation of Wnt/ß-catenin pathway, evidenced by reducing the protein levels of Wnt1, p-GSK-3ß (Ser9), and ß-catenin and preventing ß-catenin nuclear translocation. Importantly, the combination of XAV939 (an inhibitor of Wnt/ß-catenin) promoted the actions of (Ac)5GP on TNF-α-induced migration, invasion, and inflammation, further revealing the involvement of Wnt/ß-catenin pathway underlying the therapeutic effects of (Ac)5GP on TNF-α-stimulated MH7A. In vivo, (Ac)5GP relieved the progression and severity of rat collagen-induced arthritis, related to reducing the levels of IL-1ß, IL-6, IL-8, MMP-2, and MMP-9 as well as inhibiting Wnt/ß-catenin pathway in synovial tissues. Collectively, (Ac)5GP could suppress TNF-α-induced migration, invasion, and inflammation in RA FLS involving Wnt/ß-catenin pathway and (Ac)5GP might be as a candidate agent for RA treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Artritis Experimental
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Artritis Reumatoide
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Movimiento Celular
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Antirreumáticos
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Glucósidos Iridoides
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Vía de Señalización Wnt
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Fibroblastos
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Sinoviocitos
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Antiinflamatorios
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Inflammation
Año:
2021
Tipo del documento:
Article