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KMID : 0620920100420080565
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Experimental & Molecular Medicine
2010 Volume.42 No. 8 p.565 ~ p.573
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Synovial fluid of patients with rheumatoid arthritis induces α -smooth muscle actin in human adipose tissue-derived mesenchymal stem cells through a TGF-β1-dependent mechanism
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Song Hae-Young
Lee Jung-Sub
Kim Jae-Ho
Kim Min-Young
Kim Kyung-Hye
Lee Il-Hwan
Shin Sang-Hun
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Abstract
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Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. Transforming growth factor-β1 (TGF-β1) is a secreted protein that promotes differentiation of synovial fibroblasts to α-smooth muscle actin (α-SMA)-positive myofibroblasts to repair the damaged joints. Synovial fluid from patients with RA (RA-SF) induced expression of α-SMA in human adipose tissue-derived mesenchymal stem cells (hASCs). RA-SF-induced α-SMA expression was abrogated by immunodepletion of TGF-β1 from RA-SF with anti- TGF-β1 antibody. Furthermore, pretreatment of hASCs with the TGF-β type I receptor inhibitor SB431542 or lentiviral small hairpin RNA-mediated silencing of TGF-β type I receptor expression in hASCs blocked RA-SF-induced α-SMA expression. Small interfering RNA-mediated silencing of Smad2 or adenoviral overexpression of Smad7 (an inhibitory Smad isoform) completely inhibited RA-SF-stimulated α-SMA expression. These results suggest that TGF-β1 plays a pivotal role in RA-SF-induced differentiation of hASCs to α-SMA-positive cells.
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KEYWORD
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mesenchymal stem cells, rheumatoid arthritis, synovial fluid, transforming growth factor β1, α-smooth muscle actin
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