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Digestive Diseases and Sciences

Erschienen in:

01.12.2014 | Original Article

Inhibition of Endothelial Slit2/Robo1 Signaling by Thalidomide Restrains Angiogenesis by Blocking the PI3K/Akt Pathway

Erschienen in: Digestive Diseases and Sciences | Ausgabe 12/2014

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Abstract

Background

Thalidomide is effective in the treatment of angiodysplasia. The mechanisms underlying its activity may be associated with inhibition of angiogenic factors. It was recently shown that Slit2/Robo1 signaling plays a role in angiogenesis.

Purpose

The aim of this study was to explore the expression and effects of Robo1 and Slit2 in angiodysplasia and to identify the possible therapeutic mechanisms of thalidomide.

Method

Slit2 and Robo1 expression were analyzed in tissue samples and human umbilical vein endothelial cells (HUVECs) treated with thalidomide using a combination of laboratory assays that were able to detect functional activity.

Results

Slit2, Robo1 and vascular endothelial growth factor (VEGF) were strongly expressed in five angiodysplasia lesions out of seven cases, while expression was low in one out of seven normal tissues. Exposure of HUVECs to recombinant N-Slit2 resulted in an increase in VEGF levels and stimulated proliferation, migration and tube formation. These effects were blocked by an inhibitor of PI3K and thalidomide.

Conclusions

Robo1 and Slit2 may have important roles in the formation of gastrointestinal vascular malformation. High concentrations of Slit2 increased the levels of VEGF in HUVECs via signaling through the PI3K/Akt pathway—an effect that could be inhibited by thalidomide.

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Titel: Inhibition of Endothelial Slit2/Robo1 Signaling by Thalidomide Restrains Angiogenesis by Blocking the PI3K/Akt Pathway
Publikationsdatum: 01.12.2014
Erschienen in: Digestive Diseases and Sciences / Ausgabe 12/2014
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-014-3257-5

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Inhibition of Endothelial Slit2/Robo1 Signaling by Thalidomide Restrains Angiogenesis by Blocking the PI3K/Akt Pathway

Abstract

Background

Purpose

Method

Results

Conclusions

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Abstract

Background

Purpose

Method

Results

Conclusions

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