Platelet-derived growth factor stimulates the formation of Versican-Hyaluronan aggregates and pericellular matrix expansion in arterial smooth musclecells

Hyaluronan and versican-rich pericellular matrices form around arterial smo oth muscle cells (ASMC) preferentially during the detachment phase of proli feration and migration. PDGF is a potent mitogen and chemotactic agent for ASMC and also stimulates the production of extracellular matrix molecules w hich may regulate the proliferative and migratory capacity of the cells. We have examined the effect of PDGF on the formation of hyaluronan-dependent pericellular matrices, and on the synthesis and interaction of several majo r pericellular coat constituents. As demonstrated using a particle exclusio n assay, PDGF stimulated the formation of pericellular matrices and was see n both in an increased proportion of cells with a coat and a greater coat s ize. This increase was accompanied by a transient increase in hyaluronan sy nthase 2 (HAS2) expression and an increase in hyaluronan synthesis and poly mer length. PDGF also increased the synthesis of versican and link protein as measured at the mRNA and protein levels. The amount of native versican-h yaluronan aggregates and link-stabilized aggregate was also increased follo wing PDGF treatment. Time lapse imaging showed that pericellular matrix for mation occurred around trailing cell processes prior to their detachment. T hese data suggest that PDGF modulates the synthesis and organization of ASM C pericellular coat-forming molecules such as versican, hyaluronan, and lin k protein, which leads to extracellular matrix expansion and alterations in ASMC phenotype. (C) 2001 Academic Press.