Thrombospondin 1, fibronectin, and vitronectin are differentially dependent upon RAS, ERK1/2, and p38 for induction of vascular smooth muscle cell chemotaxis

Vasc Endovascular Surg. 2011 Jan;45(1):55-62. doi: 10.1177/1538574410387677.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Cattle
  • Cells, Cultured
  • Chemotaxis* / drug effects
  • Fibronectins / metabolism*
  • Humans
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / enzymology*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / enzymology*
  • Protein Kinase Inhibitors / pharmacology
  • Thrombospondin 1 / metabolism*
  • Transfection
  • Vitronectin / metabolism*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism*
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • Fibronectins
  • Protein Kinase Inhibitors
  • Thrombospondin 1
  • Vitronectin
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • ras Proteins