A novel role for inducible Fut2 in angiogenesis.
BACKGROUND
Angiogenesis plays an important role in wound healing and tumor growth. Fucosyltransferases synthesize fucosylated glycans and may play a major role in vascular biology.


OBJECTIVE
To examine the role of an alpha(1,2) fucosyltransferase (Fut2) in angiogenesis.


RESULTS
We found that Fut2 mRNA and protein expression is inducible in human dermal microvascular endothelial cells (HMVECs). After finding that Fut2 is inducible in HMVECs, we examined if Fut2 contributes to angiogenesis. We found that Fut2 null endothelial cell (EC) migration and tube formation were significantly less compared to wild type (wt) ECs. Angiogenesis was impaired in Fut2 null compared to wt mice in the mouse Matrigel plug and the sponge granuloma angiogenesis assays. To assess the characteristics of Fut2 null ECs in vivo, we performed Matrigel plug angiogenesis assays in wt mice using Fut2 null and wt mouse ECs. We found a significant decrease in Fut2 null EC incorporation in neoangiogenesis compared to wt ECs. ERK1/2 activation, fibroblast growth factor receptor2, and vascular endothelial growth factor expression were less in Fut2 null ECs, suggesting a possible mechanism of impaired angiogenesis when Fut2 is lacking.


CONCLUSIONS
These data suggest a novel role for Fut2 as a regulator of angiogenesis.
Department of Medicine, University of Michigan Medical School, Ann Arbor, 48109, USA.
Pei-Suen
PS
Tsou
Jeffrey H
JH
Ruth
Phillip L
PL
Campbell
Takeo
T
Isozaki
SolHee
S
Lee
Hubert
H
Marotte
Steven E
SE
Domino
Alisa E
AE
Koch
Mohammad A
MA
Amin
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D020405:Dermis / Q000098:blood supply; D004195:Disease Models, Animal; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005647:Fucosyltransferases / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000494:pharmacology; D007797:Laminin / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000166:cytology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D003094:Collagen; D004338:Drug Combinations; D048049:Extracellular Signal-Regulated MAP Kinases; D016222:Fibroblast Growth Factor 2; D005647:Fucosyltransferases; D006454:Hemoglobins; D053583:Interleukin-1beta; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C059485:matrigel