Skip to Main content Skip to Navigation
Journal articles

Regulation of endothelial cell cytoskeletal reorganization by a secreted frizzled-related protein-1 and frizzled 4- and frizzled 7-dependent pathway: role in neovessel formation.: molecular pathway for sFRP-1 in endothelial cell spreading

Abstract : Consistent with findings of Wnt pathway members involved in vascular cells, a role for Wnt/Frizzled signaling has recently emerged in vascular cell development. Among the few Wnt family members implicated in vessel formation in adult, Wnt7b and Frizzled 4 have been shown as involved in vessel formation in the lung and in the retina, respectively. Our previous work has shown a role for secreted Frizzled-related protein-1 (sFRP-1), a proposed Wnt signaling inhibitor, in neovascularization after an ischemic event and demonstrated its role as a potent angiogenic factor. However the mechanisms involved have not been investigated. Here, we show that sFRP-1 treatment increases endothelial cell spreading on extracellular matrix as revealed by actin stress fiber reorganization in an integrin-dependent manner. We demonstrate that sFRP-1 can interact with Wnt receptors Frizzled 4 and 7 on endothelial cells to transduce downstream to cellular machineries requiring Rac-1 activity in cooperation with GSK-3beta. sFRP-1 overexpression in endothelium specifically reversed the inactivation of GSK-3 beta and increased neovascularization in ischemia-induced angiogenesis in mouse hindlimb. This study illustrates a regulated pathway by sFRP-1 involving GSK-3beta and Rac-1 in endothelial cell cytoskeletal reorganization and in neovessel formation.
Complete list of metadatas

https://www.hal.inserm.fr/inserm-00508525
Contributor : Christelle Boullé <>
Submitted on : Wednesday, August 4, 2010 - 10:51:17 AM
Last modification on : Wednesday, February 7, 2018 - 2:52:06 PM
Long-term archiving on: : Thursday, December 1, 2016 - 8:48:23 PM

Files

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Pascale Dufourcq, Lionel Leroux, Jérome Ezan, Betty Descamps, Jean-Marie Daniel Lamazière, et al.. Regulation of endothelial cell cytoskeletal reorganization by a secreted frizzled-related protein-1 and frizzled 4- and frizzled 7-dependent pathway: role in neovessel formation.: molecular pathway for sFRP-1 in endothelial cell spreading. American Journal of Pathology, American Society for Investigative Pathology, 2008, 172 (1), pp.37-49. ⟨10.2353/ajpath.2008.070130⟩. ⟨inserm-00508525⟩

Share

Metrics

Record views

199