Wnt1 and Wnt5a affect endothelial proliferation and capillary length; Wnt2 does not.
Blood vessel growth is critical for embryonic development and contributes to pathologies including cancer and diabetic retinopathy. A growing body of evidence suggests that signaling via the Wnt/beta-catenin pathway contributes to angiogenesis, and that paracrine Wnt signaling might alter endothelial cell function. To test the hypothesis that Wnt signaling promotes endothelial cell proliferation and vessel growth, we treated bovine aortic endothelial cells with Wnt1, Wnt2 and Wnt5a derived from coculture with Wnt-expressing fibroblasts. Endothelial cells cultured in the presence of Wnt1 displayed increased Wnt/beta-catenin signaling, proliferation and capillary stability in vitro. Wnt5a, which primarily signals via an alternate Wnt pathway, the Wnt/Ca(++) pathway, decreased both cell number and capillary length. Wnt2, which in other cell types activates the Wnt/beta-catenin pathway, did not activate signaling, affect cell number or increase capillary length. These results suggest that Wnt/beta-catenin and Wnt/Ca(++) signals might have opposing effects on angiogenesis.
Goodwin
Anne M
AM
The Schepens Eye Research Institute and the Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA.
Kitajewski
Jan
J
D'Amore
Patricia A
PA
D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000254:growth & development; D002417:Cattle; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051154:Wnt2 Protein / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D011994:Recombinant Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; C495245:Wnt1 protein, rat; D051154:Wnt2 Protein; C491837:Wnt5a protein, rat