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.
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.
Song
Hae Young
HY
Medical Research Center for Ischemic Tissue Regeneration, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan, Korea.
Kim
Min Young
MY
Kim
Kyung Hye
KH
Lee
Il Hwan
IH
Shin
Sang Hun
SH
Lee
Jung Sub
JS
Kim
Jae Ho
JH
D000199:Actins / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D022502:Stress Fibers / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
C541116:ACTA2 protein, human; D000199:Actins; D049368:Receptors, Lysophosphatidic Acid; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1