title: 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.
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.
authors.affiliation: Medical Research Center for Ischemic Tissue Regeneration, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan, Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Song
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Kyung Hye
authors.initials: KH
authors.lastname: Kim
authors.forename: Il Hwan
authors.initials: IH
authors.lastname: Lee
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Shin
authors.forename: Jung Sub
authors.initials: JS
authors.lastname: Lee
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
mesh_terms: 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*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D049368:Receptors, Lysophosphatidic Acid; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1