Abstract
The extracellular matrix molecule hyaluronan was found to suppress platelet-derived growth factor (PDGF) beta-receptor activation and PDGF-BB-induced migration of primary human dermal fibroblasts. The suppressive effect of hyaluronan was neutralized by a monoclonal antibody that specifically inhibits hyaluronan binding to its receptor CD44. Moreover, co-immunoprecipitation experiments showed that the PDGF beta-receptor and CD44 can form a complex. Interestingly, the inhibitory effect of hyaluronan on PDGF beta-receptor activation was not seen in the presence of the tyrosine phosphatase inhibitor pervanadate. Our observations suggest that hyaluronan suppresses PDGF beta-receptor activation by recruiting a CD44-associated tyrosine phosphatase to the receptor.
Highlights
platelet-derived growth factor (PDGF)-BB Induces Migration and Stimulates Hyaluronan Production by Human Dermal Fibroblasts—Because both PDGF-BB and hyaluronan have been implicated in cell migration [4, 22], we investigated the importance of these molecules for migration of human dermal fibroblasts
We show in this study that hyaluronan inhibits PDGF-BBinduced activation of PDGFR and cell motility
The monoclonal antibody Hermes-1, which blocks the binding of hyaluronan to CD44, restored PDGF -receptor activation and motility, indicating that CD44 mediates the inhibiting effect on PDGFR
Summary
Growth factors play a central role in cell migration during both normal and pathological conditions, including embryogenesis, wound healing, and tumor invasion. In this regard, platelet-derived growth factor (PDGF)2-BB is a powerful stimulator of the migration of mesenchymal cells, such as fibroblasts [21,22,23]. Hyaluronan-inhibited PDGFR Activation and Fibroblast Motility by a number of protein-tyrosine phosphatases (PTPs), which thereby affect downstream signaling of the receptors [25]. We investigated the possibility that hyaluronan affects PDGF-BB-induced cell migration of human dermal fibroblast cultures
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