IQGAP1 regulates hyaluronan-mediated fibroblast motility and proliferation

IQGAP1, an essential scaffolding protein, forms a complex with the hyaluronan receptor CD44. In this study, we have examined the importance of IQGAP1 for hyaluronan-mediated fibroblast migration and proliferation. Hyaluronan induced formation of F-actin fibers and focal adhesions, which was dependent on IQGAP1. IQGAP1 was required for hyaluronan- but not for platelet-derived growth factor (PDGF)-BB-induced cell migration, and was required for both hyaluronan- and PDGF-BB-mediated fibroblast proliferation, but not for proliferation induced by 10% fetal bovine serum. Depletion of IQGAP1 suppressed hyaluronan-induced activation of Rac1 and enhanced the activation of RhoA. Taken together, these findings indicate important roles for IQGAP1 in hyaluronan‐stimulated migration and proliferation of fibroblasts.

► IQGAP1 interacts with hyaluronan-activated CD44 in human fibroblast cultures.
► IQGAP1 expression is required for hyaluronan-stimulated migration and proliferation.
► The hyaluronan-induced activation of Rac1 is dependent on IQGAP1.
► IQGAP1 plays an important role in hyaluronan-induced actin cytoskeleton rearrangments.