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Hyaluronic acid promotes angiogenesis by inducing RHAMM-TGFβ receptor interaction via CD44-PKCδ
- Hyaluronic acid promotes angiogenesis by inducing RHAMM-TGFβ receptor interaction via CD44-PKCδ
- Park D.; Kim Y.; Kim H.; Kim K.; Lee Y.-S.; Choe J.; Hahn J.-H.; Lee H.; Jeon J.; Choi C.; Kim Y.-M.; Jeoung D.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Molecules and Cells
- vol. 33, no. 6, pp. 563 - 574
- SCI; SCIE; SCOPUS; KCI
- Hyaluronic acid (HA) has been shown to promote angio-genesis. However, the mechanism behind this effect remains largely unknown. Therefore, in this study, the mechanism of HA-induced angiogenesis was examined. CD44 and PKCδ were shown to be necessary for induction of the receptor for HA-mediated cell motility (RHAMM), a HA-binding protein. RHAMM was necessary for HA-pro-moted cellular invasion and endothelial cell tube formation. Cytokine arrays showed that HA induced the expression of plasminogen activator-inhibitor-1 (PAI), a downstream target of TGFβ receptor signaling. The induction of PAI-1 was dependent on CD44 and PKCδ. HA also induced an interaction between RHAMM and TGFβ receptor I, and induction of PAI-1 was dependent on RHAMM and TGFβ receptor I. Histone deacetylase 3 (HDAC3), which is decreased by HA via rac1, reduced induction of plasminogen activator inhibitor-1 (PAI-1) by HA. ERK, which interacts with RHAMM, was necessary for induction of PAI-1 by HA. Snail, a downstream target of TGFβ signaling, was also necessary for induction of PAI-1. The down regulation of PAI-1 prevented HA from enhancing endothelial cell tube formation and from inducing expression of angiogenic factors, such as ICAM-1, VCAM-1 and MMP-2. HDAC3 also exerted reduced expression of MMP-2. In this study, we provide a novel mechanism of HA-promoted angiogenesis, which involved RHAMM-TGFβRI signaling necessary for induction of PAI-1. © 2012 KSMCB.
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