Andrea Taddei

Publications (4)44.31 Total impact

• Article: Overlapping and divergent signaling pathways of N-cadherin and VE-cadherin in endothelial cells.

  Costanza Giampietro, Andrea Taddei, Monica Corada, Gian Maria Sarra-Ferraris, Myriam Alcalay, Ugo Cavallaro, Fabrizio Orsenigo, Maria Grazia Lampugnani, Elisabetta Dejana
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  ABSTRACT: Endothelial cells (ECs) express 2 members of the cadherin family, VE and N-cadherin. Although VE-cadherin induces EC homotypic adhesion, N-cadherin function in ECs remains largely unknown. EC-specific inactivation of either VE or N-cadherin leads to early fetal lethality suggesting that these cadherins play a nonredundant role in vascular development. We report here that VE-cadherin negatively controls junctional localization and expression of N-cadherin by limiting p120-catenin availability and reducing β-catenin transcriptional activity. Using EC lines expressing either VE or N-cadherin we found that both cadherins inhibit cell proliferation and apoptosis. Both trigger the phosphatidylinositol-3-OH-kinase (PI3K)-AKT-Forkhead-box protein-O1 (FoxO1) pathway and reduce β-catenin transcriptional activity. The extent of signaling correlates with the total level of cadherins regardless of the type of cadherin expressed. In contrast, basal and fibroblast growth factor (FGF)-induced cell motility is promoted by N-cadherin and strongly inhibited by VE-cadherin. This opposite effect is partly because of the ability of VE-cadherin to associate with FGF receptor and the density-enhanced phosphatase-1 (Dep-1) which, in turn, inhibits receptor signaling. We conclude that VE and N-cadherin have both additive and divergent effects on ECs. Differences in signaling are due, in part, to cadherin association with growth factor receptors and modulation of their downstream signaling.
  Blood 03/2012; 119(9):2159-70. · 9.90 Impact Factor
• Source

  Available from: Cathrin Jacqueline Czupalla

  Article: Wnt/beta-catenin signaling controls development of the blood-brain barrier.

  Stefan Liebner, Monica Corada, Thorsten Bangsow, Jane Babbage, Andrea Taddei, Cathrin J Czupalla, Marco Reis, Angelina Felici, Hartwig Wolburg, Marcus Fruttiger, Makoto M Taketo, Harald von Melchner, Karl Heinz Plate, Holger Gerhardt, Elisabetta Dejana
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  ABSTRACT: The blood-brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/beta-catenin (beta-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of beta-cat in vivo enhances barrier maturation, whereas inactivation of beta-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of beta-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of beta-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of beta-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown.
  The Journal of Cell Biology 12/2008; 183(3):409-17. · 10.26 Impact Factor
• Source

  Available from: ifom-firc.it

  Article: Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5.

  Andrea Taddei, Costanza Giampietro, Annarita Conti, Fabrizio Orsenigo, Ferruccio Breviario, Valentina Pirazzoli, Michael Potente, Christopher Daly, Stefanie Dimmeler, Elisabetta Dejana
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  ABSTRACT: Intercellular junctions mediate adhesion and communication between adjoining cells. Although formed by different molecules, tight junctions (TJs) and adherens junctions (AJs) are functionally and structurally linked, but the signalling pathways behind this interaction are unknown. Here we describe a cell-specific mechanism of crosstalk between these two types of structure. We show that endothelial VE-cadherin at AJs upregulates the gene encoding the TJ adhesive protein claudin-5. This effect requires the release of the inhibitory activity of forkhead box factor FoxO1 and the Tcf-4-beta-catenin transcriptional repressor complex. Vascular endothelial (VE)-cadherin acts by inducing the phosphorylation of FoxO1 through Akt activation and by limiting the translocation of beta-catenin to the nucleus. These results offer a molecular basis for the link between AJs and TJs and explain why VE-cadherin inhibition may cause a marked increase in permeability.
  Nature Cell Biology 08/2008; 10(8):923-34. · 19.49 Impact Factor
• Article: Foxs and Ets in the transcriptional regulation of endothelial cell differentiation and angiogenesis.

  Elisabetta Dejana, Andrea Taddei, Anna M Randi
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  ABSTRACT: During tumour growth the surrounding vasculature forms new vessels which penetrate into the stroma and bring oxygen and nutrients to the proliferating cancer cells. The ability to control and reduce this phenomenon may have important therapeutic implications. Angiogenesis is a complex event which requires endothelial cell sprouting, lumen formation, tubulogenesis and is regulated by the coordinated action of different transcription factors. Studies on promoters of endothelial cell-specific genes or gene inactivation experiments reveal the extreme complexity of the system. Many transcription factors are implicated in vascular development and the majority are not endothelial-specific. Their interaction leads to endothelial cell differentiation and acquisition of arterial, venous and lymphatic properties. Two large families of transcription factors, Foxs and Ets, play a major role in these events. They participate in both embryonic and adult angiogenesis. The FoxO subgroup regulates the correct organization of the vascular system, controlling excessive endothelial growth and inducing apoptosis both in embryos and adult mice. Ets factors participate in early endothelial differentiation and angiogenesis. Many members of this family are expressed very early in the developing vasculature and Ets consensus binding domains are present in essentially all endothelial cell-specific gene promoters. In this review we discuss the overall transcriptional regulation of vascular development with a particular focus on some specific members of these two families considered important in the formation and maintenance of the vascular network.
  Biochimica et Biophysica Acta 07/2007; 1775(2):298-312. · 4.66 Impact Factor