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A novel role for inducible Fut2 in angiogenesis

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Abstract

Rationale

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.

Methods and 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.

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Acknowledgments

We are thankful to Sivakumar Nallasivam who helped us to perform immunofluorescence with Matrigel plug sections. This study was supported by funds from the Veterans’ Administration Research Service (AEK) and the Frederick G.L. Huetwell and William D. Robinson Professorship (AEK). Additional support included funds from National Institute of Health grants AI40987 (AEK), HL58695 (AEK), AR48267 (AEK), and AR052482 (MAA).

Ethical Standards

The experiments conducted in this manuscript comply with the current laws of the United States.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA

    Pei-Suen Tsou, Jeffrey H. Ruth, Phillip L. Campbell, Takeo Isozaki, SolHee Lee, Hubert Marotte, Alisa E. Koch & Mohammad A. Amin

  2. Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA

    Steven E. Domino

  3. Veteran’s Administration, Ann Arbor, MI, 48109, USA

    Alisa E. Koch

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  1. Pei-Suen Tsou
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  2. Jeffrey H. Ruth
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Corresponding author

Correspondence to Mohammad A. Amin.

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Tsou, PS., Ruth, J.H., Campbell, P.L. et al. A novel role for inducible Fut2 in angiogenesis. Angiogenesis 16, 195–205 (2013). https://doi.org/10.1007/s10456-012-9312-y

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  • DOI: https://doi.org/10.1007/s10456-012-9312-y

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