Thrombospondin-1-induced vascular smooth muscle cell migration is dependent on the hyaluronic acid receptor CD44.
BACKGROUND
Thrombospondin-1 (TSP-1) induces vascular smooth muscle cell (VSMC) migration after arterial injury. TSP-1 up-regulates hyaluronic acid (HyA)-inducing genes in VSMCs. HyA also induces VSMC migration. Our hypothesis was that TSP-1-induced VSMC migration is dependent on the CD44 receptor, and that HyA and TSP-1 share migratory signaling pathways.


METHODS
VSMC migration was assessed using TSP-1, HyA, or serum-free medium as chemoattractants. VSMCs were treated with inhibitors to CD44, Ras, phosphatidylinositol-3 kinase, Raf-1 kinase, or c-SRC. TSP-1- and HyA-induced epidermal growth factor receptor (EGFR) activity was determined by enzyme-linked immunosorbent assay. Comparisons were made by the Student t test and a P value less than .05 was considered significant.


RESULTS
Inhibiting CD44 reduced TSP-1- and HyA-induced migration. Phosphatidylinositol-3 kinase and c-SRC inhibitors prevented TSP-1- and HyA-induced migration, whereas Ras and Raf-1 kinase inhibitors only affected TSP-1. TSP-1 and HyA activate the EGFR.


CONCLUSIONS
TSP-1- and HYA-induced migration share some of the same signaling pathways and the EGFR/CD44 receptors may be a common link.
Maier
Kristopher G
KG
Division of Vascular Surgery and Endovascular Services, SUNY Upstate Medical University, Syracuse, NY 13210, USA. maierk@upstate.edu
Sadowitz
Benjamin
B
Cullen
Sarah
S
Han
Xuan
X
Gahtan
Vivian
V
D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002417:Cattle; D002465:Cell Movement / Q000502:physiology*; D002633:Chemotaxis / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000502:physiology; D018960:Hyaluronan Receptors / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D019908:Proto-Oncogene Proteins c-raf / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D019700:Thrombospondin 1 / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology; D018909:src Homology Domains; D019061:src-Family Kinases
D018960:Hyaluronan Receptors; D019700:Thrombospondin 1; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D019908:Proto-Oncogene Proteins c-raf