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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