Vascular smooth muscle cell migration induced by domains of thrombospondin-1 is differentially regulated
pmid: 21906719
Vascular smooth muscle cell migration induced by domains of thrombospondin-1 is differentially regulated
Thrombospondin-1 (TSP-1) stimulates vascular smooth muscle cell (VSMC) migration via defined intracellular signaling pathways. The aim of this study was to examine the signaling pathways whereby TSP-1 folded domains (amino-terminal [NH(2)], procollagen homology [PCH], all 3 type 1 repeats [3TSR], and a single recombinant protein containing the 3rd type 2 repeat, the type 3 repeats, and the carboxyl-terminal [E3T3C1]) induce VSMC migration.Quiescent VSMCs were pretreated with serum-free media or inhibitors: PP2 (c-Src), LY294002 (phosphatidylinositol 3-kinase), FPT (Ras), Y27632 (Rho kinase), SB202190 (p38 kinase), and PD98059 (extracellular signal-regulated kinase). Migration induced by serum-free media, TSP-1, NH(2), PCH, 3TSR, and E3T3C1 was assessed using a modified Boyden chamber.TSP-1, NH(2), 3TSR, and E3T3C1 induced VSMC chemotaxis (P .05). PP2, FPT, SB202190, and PD98059 attenuated chemotaxis stimulated by TSP-1, NH(2), 3TSR, and E3T3C1 (P .05) chemotaxis. Y27632 inhibited NH(2)-induced, 3TSR-induced, and E3T3C1-induced (P .05) induced chemotaxis.TSP-1 folded domains are differentially dependent on intracellular signaling pathways to induce migration.
- United States Department of Veterans Affairs United States
- Beth Israel Deaconess Medical Center United States
- SUNY Upstate Medical University United States
Flavonoids, Protein Folding, Pyridines, Chemotaxis, Morpholines, Myocytes, Smooth Muscle, Imidazoles, Organophosphonates, Amides, Muscle, Smooth, Vascular, Thrombospondin 1, Pyrimidines, Cell Movement, Chromones, Humans, Enzyme Inhibitors, Cells, Cultured, Signal Transduction
Flavonoids, Protein Folding, Pyridines, Chemotaxis, Morpholines, Myocytes, Smooth Muscle, Imidazoles, Organophosphonates, Amides, Muscle, Smooth, Vascular, Thrombospondin 1, Pyrimidines, Cell Movement, Chromones, Humans, Enzyme Inhibitors, Cells, Cultured, Signal Transduction
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