Thrombospondin 1, Fibronectin, and Vitronectin are Differentially Dependent Upon RAS, ERK1/2, and p38 for Induction of Vascular Smooth Muscle Cell Chemotaxis
Copyright policy )Thrombospondin 1, Fibronectin, and Vitronectin are Differentially Dependent Upon RAS, ERK1/2, and p38 for Induction of Vascular Smooth Muscle Cell Chemotaxis
Background: Thrombospondin 1 (TSP-1), fibronectin (Fn), and vitronectin (Vn) promote vascular smooth muscle cell (VSMC) chemotaxis through a variety of second messenger systems, including Ras, ERK1/2, and p38. Hypothesis: Ras, ERK1/2, and p38 differentially affect TSP-1-, Fn-, and Vn-induced VSMC chemotaxis. Methods: Bovine VSMCs were transfected with Ras N17 or treated with the following inhibitors: a farnesyl protein transferase (FPT) inhibitor, PD098059 (ERK1/2 inhibitor), or SB202190 (p38 inhibitor). Thrombospondin 1, Fn, and Vn were used as chemoattractants. Results were analyzed by analysis of variance (ANOVA) with post hoc testing (P < .05). Results: Ras N17 transfection or FPT inhibitor treatment inhibited TSP-1-, Fn-, and Vn-induced chemotaxis. PD098059 or SB202190 resulted in more inhibition of VSMC migration to TSP-1 than to Fn or Vn. Conclusions: Ras appears equally relevant in the signal transduction pathways of TSP-1-, Fn-, and Vn-induced VSMC chemotaxis. Thrombospondin 1-induced migration is more dependent upon ERK1/2 and p38 than Fn- or Vn-included migration.
- State University of New York at Potsdam United States
- United States Department of Veterans Affairs United States
- VA Connecticut Healthcare System United States
- SUNY Upstate Medical University United States
- Temple University United States
Mitogen-Activated Protein Kinase 1, Analysis of Variance, Mitogen-Activated Protein Kinase 3, Chemotaxis, Myocytes, Smooth Muscle, Transfection, p38 Mitogen-Activated Protein Kinases, Muscle, Smooth, Vascular, Fibronectins, Thrombospondin 1, ras Proteins, Animals, Humans, Cattle, Vitronectin, Protein Kinase Inhibitors, Cells, Cultured
Mitogen-Activated Protein Kinase 1, Analysis of Variance, Mitogen-Activated Protein Kinase 3, Chemotaxis, Myocytes, Smooth Muscle, Transfection, p38 Mitogen-Activated Protein Kinases, Muscle, Smooth, Vascular, Fibronectins, Thrombospondin 1, ras Proteins, Animals, Humans, Cattle, Vitronectin, Protein Kinase Inhibitors, Cells, Cultured
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