TY - JOUR
T1 - Proteomic profiling of bone marrow mesenchymal stem cells upon transforming growth factor β1 stimulation
AU - Wang, Daojing
AU - Park, Jennifer S.
AU - Chu, Julia S F
AU - Krakowski, Ari
AU - Luo, Kunxin
AU - Chen, David J.
AU - Li, Song
PY - 2004/10/15
Y1 - 2004/10/15
N2 - Bone marrow mesenchymal stem cells (MSCs) can differentiate into different types of cells and have tremendous potential for cell therapy and tissue engineering. Transforming growth factor β1 (TGF-β) plays an important role in cell differentiation and vascular remodeling. We showed that TGF-β induced cell morphology change and an increase in actin fibers in MSCs. To determine the global effects of TGF-β on MSCs, we employed a proteomic strategy to analyze the effect of TGF-β on the human MSC proteome. By using two-dimensional gel electrophoresis and electrospray ionization coupled to quadrupole/time-of-flight tandem mass spectrometers, we have generated a proteome reference map of MSCs, and we identified ∼30 proteins with an increase or decrease in expression or phosphorylation in response to TGF-β. The proteins regulated by TGF-β included cytoskeletal proteins, matrix synthesis proteins, membrane proteins, metabolic enzymes, etc. TGF-β increased the expression of smooth muscle α-actin and decreased the expression of gelsolin. Overexpression of gelsolin inhibited TGF-β-induced assembly of smooth muscle α-actin; on the other hand, knocking down gelsolin expression enhanced the assembly of α-actin and actin filaments without significantly affecting α-actin expression. These results suggest that TGF-β coordinates the increase of α-actin and the decrease of gelsolin to promote MSC differentiation. This study demonstrates that proteomic tools are valuable in studying stem cell differentiation and elucidating the underlying molecular mechanisms.
AB - Bone marrow mesenchymal stem cells (MSCs) can differentiate into different types of cells and have tremendous potential for cell therapy and tissue engineering. Transforming growth factor β1 (TGF-β) plays an important role in cell differentiation and vascular remodeling. We showed that TGF-β induced cell morphology change and an increase in actin fibers in MSCs. To determine the global effects of TGF-β on MSCs, we employed a proteomic strategy to analyze the effect of TGF-β on the human MSC proteome. By using two-dimensional gel electrophoresis and electrospray ionization coupled to quadrupole/time-of-flight tandem mass spectrometers, we have generated a proteome reference map of MSCs, and we identified ∼30 proteins with an increase or decrease in expression or phosphorylation in response to TGF-β. The proteins regulated by TGF-β included cytoskeletal proteins, matrix synthesis proteins, membrane proteins, metabolic enzymes, etc. TGF-β increased the expression of smooth muscle α-actin and decreased the expression of gelsolin. Overexpression of gelsolin inhibited TGF-β-induced assembly of smooth muscle α-actin; on the other hand, knocking down gelsolin expression enhanced the assembly of α-actin and actin filaments without significantly affecting α-actin expression. These results suggest that TGF-β coordinates the increase of α-actin and the decrease of gelsolin to promote MSC differentiation. This study demonstrates that proteomic tools are valuable in studying stem cell differentiation and elucidating the underlying molecular mechanisms.
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U2 - 10.1074/jbc.M407368200
DO - 10.1074/jbc.M407368200
M3 - Article
C2 - 15302865
AN - SCOPUS:6344281040
SN - 0021-9258
VL - 279
SP - 43725
EP - 43734
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 42
ER -