Differential uPAR recruitment in caveolar-lipid rafts by GM1 and GM3 gangliosides regulates endothelial progenitor cells angiogenesis

Francesca Margheri, Laura Papucci, Nicola Schiavone, Riccardo D'Agostino, Silvana Trigari, Simona Serratì, Anna Laurenzana, Alessio Biagioni, Cristina Luciani, Anastasia Chillà, Elena Andreucci, Tommaso Del Rosso, Giancarlo Margheri, Mario Del Rosso, Gabriella Fibbi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Gangliosides and the urokinase plasminogen activator receptor (uPAR) tipically partition in specialized membrane microdomains called lipid-rafts. uPAR becomes functionally important in fostering angiogenesis in endothelial progenitor cells (EPCs) upon recruitment in caveolar-lipid rafts. Moreover, cell membrane enrichment with exogenous GM1 ganglioside is pro-angiogenic and opposite to the activity of GM3 ganglioside. On these basis, we first checked the interaction of uPAR with membrane models enriched with GM1 or GM3, relying on the adoption of solid-supported mobile bilayer lipid membranes with raft-like composition formed onto solid hydrophilic surfaces, and evaluated by surface plasmon resonance (SPR) the extent of uPAR recruitment. We estimated the apparent dissociation constants of uPAR-GM1/GM3 complexes. These preliminary observations, indicating that uPAR binds preferentially to GM1-enriched biomimetic membranes, were validated by identifying a pro-angiogenic activity of GM1-enriched EPCs, based on GM1-dependent uPAR recruitment in caveolar rafts. We have observed that addition of GM1 to EPCs culture medium promotes matrigel invasion and capillary morphogenesis, as opposed to the anti-angiogenesis activity of GM3. Moreover, GM1 also stimulates MAPKinases signalling pathways, typically associated with an angiogenesis program. Caveolar-raft isolation and Western blotting of uPAR showed that GM1 promotes caveolar-raft partitioning of uPAR, as opposed to control and GM3-challenged EPCs. By confocal microscopy, we have shown that in EPCs uPAR is present on the surface in at least three compartments, respectively, associated to GM1, GM3 and caveolar rafts. Following GM1 exogenous addition, the GM3 compartment is depleted of uPAR which is recruited within caveolar rafts thereby triggering angiogenesis.

Original languageEnglish
Pages (from-to)113-123
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Fingerprint

G(M3) Ganglioside
Urokinase Plasminogen Activator Receptors
G(M1) Ganglioside
Lipids
Endothelial Progenitor Cells
Membrane Microdomains
Biomimetics
Foster Home Care
Membranes
Surface Plasmon Resonance
Gangliosides
Lipid Bilayers
Membrane Lipids
Morphogenesis
Confocal Microscopy
Culture Media

Keywords

  • Angiogenesis
  • Caveolar-lipid rafts
  • Endothelial colony-forming cells
  • Endothelial progenitor cells
  • GM1
  • GM3
  • Lipid rafts
  • MAPKinases
  • UPAR

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Differential uPAR recruitment in caveolar-lipid rafts by GM1 and GM3 gangliosides regulates endothelial progenitor cells angiogenesis. / Margheri, Francesca; Papucci, Laura; Schiavone, Nicola; D'Agostino, Riccardo; Trigari, Silvana; Serratì, Simona; Laurenzana, Anna; Biagioni, Alessio; Luciani, Cristina; Chillà, Anastasia; Andreucci, Elena; Del Rosso, Tommaso; Margheri, Giancarlo; Del Rosso, Mario; Fibbi, Gabriella.

In: Journal of Cellular and Molecular Medicine, Vol. 19, No. 1, 01.01.2015, p. 113-123.

Research output: Contribution to journalArticle

Margheri, F, Papucci, L, Schiavone, N, D'Agostino, R, Trigari, S, Serratì, S, Laurenzana, A, Biagioni, A, Luciani, C, Chillà, A, Andreucci, E, Del Rosso, T, Margheri, G, Del Rosso, M & Fibbi, G 2015, 'Differential uPAR recruitment in caveolar-lipid rafts by GM1 and GM3 gangliosides regulates endothelial progenitor cells angiogenesis', Journal of Cellular and Molecular Medicine, vol. 19, no. 1, pp. 113-123. https://doi.org/10.1111/jcmm.12410
Margheri, Francesca ; Papucci, Laura ; Schiavone, Nicola ; D'Agostino, Riccardo ; Trigari, Silvana ; Serratì, Simona ; Laurenzana, Anna ; Biagioni, Alessio ; Luciani, Cristina ; Chillà, Anastasia ; Andreucci, Elena ; Del Rosso, Tommaso ; Margheri, Giancarlo ; Del Rosso, Mario ; Fibbi, Gabriella. / Differential uPAR recruitment in caveolar-lipid rafts by GM1 and GM3 gangliosides regulates endothelial progenitor cells angiogenesis. In: Journal of Cellular and Molecular Medicine. 2015 ; Vol. 19, No. 1. pp. 113-123.
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