期刊
EXPERIMENTAL AND MOLECULAR MEDICINE
卷 42, 期 8, 页码 565-573出版社
NATURE PUBLISHING GROUP
DOI: 10.3858/emm.2010.42.8.057
关键词
mesenchymal stem cells; rheumatoid arthritis; synovial fluid; transforming growth factor beta 1; alpha-smooth muscle actin
资金
- Pusan National University (PNU) [PNU-2008-059-7000]
Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. Transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1 from RA-SF with anti-TGF-beta 1 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-beta 1 plays a pivotal role in RA-SF-induced differentiation of hASCs to alpha-SMA-positive cells.
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