Synovial fluid of patients with rheumatoid arthritis induces alpha-smooth muscle actin in human adipose tissue-derived mesenchymal stem cells through a TGF-beta1-dependent mechanism
Experimental & Molecular Medicine
; : 565-573, 2010.
Article
de En
| WPRIM
| ID: wpr-200109
Bibliothèque responsable:
WPRO
ABSTRACT
Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. Transforming growth factor-beta1 (TGF-beta1) is a secreted protein that promotes differentiation of synovial fibroblasts to alpha-smooth muscle actin (alpha-SMA)-positive myofibroblasts to repair the damaged joints. Synovial fluid from patients with RA (RA-SF) induced expression of alpha-SMA in human adipose tissue-derived mesenchymal stem cells (hASCs). RA-SF-induced alpha-SMA expression was abrogated by immunodepletion of TGF-beta1 from RA-SF with anti-TGF-beta1 antibody. Furthermore, pretreatment of hASCs with the TGF-beta type I receptor inhibitor SB431542 or lentiviral small hairpin RNA-mediated silencing of TGF-beta type I receptor expression in hASCs blocked RA-SF-induced alpha-SMA expression. Small interfering RNA-mediated silencing of Smad2 or adenoviral overexpression of Smad7 (an inhibitory Smad isoform) completely inhibited RA-SF-stimulated alpha-SMA expression. These results suggest that TGF-beta1 plays a pivotal role in RA-SF-induced differentiation of hASCs to alpha-SMA-positive cells.
Mots clés
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Polyarthrite rhumatoïde
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Synovie
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Transduction du signal
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Tissu adipeux
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Actines
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Fibres de stress
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Récepteurs à l'acide phosphatidique
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Protéine Smad2
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Facteur de croissance transformant bêta-1
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Cellules souches mésenchymateuses
Limites du sujet:
Humans
langue:
En
Texte intégral:
Experimental & Molecular Medicine
Année:
2010
Type:
Article