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.
10.3858/emm.2010.42.8.057
- Author:
Hae Young SONG
1
;
Min Young KIM
;
Kyung Hye KIM
;
Il Hwan LEE
;
Sang Hun SHIN
;
Jung Sub LEE
;
Jae Ho KIM
Author Information
1. Medical Research Center for Ischemic Tissue Regeneration, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 626-870, Korea. jhkimst@pusan.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
mesenchymal stem cells;
rheumatoid arthritis;
synovial fluid;
transforming growth factor beta1;
alpha-smooth muscle actin
- MeSH:
Actins/*metabolism;
Adipose Tissue/*cytology;
Arthritis, Rheumatoid/*metabolism;
Humans;
Mesenchymal Stem Cells/*metabolism;
Receptors, Lysophosphatidic Acid/metabolism;
Signal Transduction;
Smad2 Protein/metabolism;
Stress Fibers/metabolism;
Synovial Fluid/*metabolism;
Transforming Growth Factor beta1/*metabolism
- From:Experimental & Molecular Medicine
2010;42(8):565-573
- CountryRepublic of Korea
- Language:English
-
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.
