| Naslov: | The role of heparan sulfate and neuropilin 2 in VEGFA signaling in human endothelial tip cells and non-tip cells during angiogenesis in vitro |
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| Avtorji: | ID Dallinga, Marchien G. (Avtor)
ID Habani, Yasmin I. (Avtor)
ID Schimmel, Alinda W. M. (Avtor)
ID Dallinga-Thie, Geesje M. (Avtor)
ID Noorden, Cornelis J. F. van (Avtor)
ID Klaassen, Ingeborg (Avtor)
ID Schlingemann, Reinier O. (Avtor) |
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| Datoteke: |  URL - Izvorni URL, za dostop obiščite https://www.mdpi.com/2073-4409/10/4/926
 PDF - Predstavitvena datoteka, prenos (3,24 MB)
MD5: 9D87E37BEDFE2597F561A4702DAF0767
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| Jezik: | Angleški jezik |
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| Tipologija: | 1.01 - Izvirni znanstveni članek |
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| Organizacija: |  NIB - Nacionalni inštitut za biologijo
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| Povzetek: | During angiogenesis, vascular endothelial growth factor A (VEGFA) regulates endothelial cell (EC) survival, tip cell formation, and stalk cell proliferation via VEGF receptor 2 (VEGFR2). VEGFR2 can interact with VEGFR2 co-receptors such as heparan sulfate proteoglycans (HSPGs) and neuropilin 2 (NRP2), but the exact roles of these co-receptors, or of sulfatase 2 (SULF2), an enzyme that removes sulfate groups from HSPGs and inhibits HSPG-mediated uptake of very low density lipoprotein (VLDL), in angiogenesis and tip cell biology are unknown. In the present study, we investigated whether the modulation of binding of VEGFA to VEGFR2 by knockdown of SULF2 or NRP2 affects sprouting angiogenesis, tip cell formation, proliferation of non-tip cells, and EC survival, or uptake of VLDL. To this end, we employed VEGFA splice variant 121, which lacks an HSPG binding domain, and VEGFA splice variant 165, which does have this domain, in in vitro models of angiogenic tip cells and vascular sprouting. We conclude that VEGFA165 and VEGFA121 have similar inducing effects on tip cells and sprouting in vitro, and that the binding of VEGFA165 to HSPGs in the extracellular matrix does not seem to play a role, as knockdown of SULF2 did not alter these effects. Co-binding of NRP2 appears to regulate VEGFA–VEGFR2-induced sprout initiation, but not tip cell formation. Finally, as the addition of VLDL increased sprout formation but not tip cell formation, and as VLDL uptake was limited to non-tip cells, our findings suggest that VLDL plays a role in sprout formation by providing biomass for stalk cell proliferation. |
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| Ključne besede: | endothelial cells, angiogenesis, VEGFA, tip cells, SULF2, NRP2, HSPG |
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| Status publikacije: | Objavljeno |
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| Verzija publikacije: | Objavljena publikacija |
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| Datum objave: | 16.04.2021 |
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| Leto izida: | 2021 |
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| Št. strani: | str. 1-17 |
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| Številčenje: | Vol. 10, iss. 4 |
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| PID: | 20.500.12556/DiRROS-19472  |
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| UDK: | 577.2 |
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| ISSN pri članku: | 2073-4409 |
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| DOI: | 10.3390/cells10040926 |
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| COBISS.SI-ID: | 61567747 |
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| Opomba: | Nasl. z nasl. zaslona;
Opis vira z dne 3. 5. 2021;
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| Datum objave v DiRROS: | 19.07.2024 |
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| Število ogledov: | 266 |
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| Število prenosov: | 204 |
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| Metapodatki: |    |
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