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Xiong, Y.* ; Scerbo, M.J. ; Seelig, A. ; Volta, F. ; O'Brien, N. ; Dicker, A.* ; Padula, D. ; Lickert, H. ; Gerdes, J.M. ; Berggren, P.O.*

Islet vascularization is regulated by primary endothelial cilia via VEGF-A-dependent signaling.

eLife 9:e56914 (2020)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Islet vascularization is essential for intact islet function and glucose homeostasis. We have previously shown that primary cilia directly regulate insulin secretion. However, it remains unclear whether they are also implicated in islet vascularization. At eight weeks, murine Bbs4-/-islets show significantly lower intra-islet capillary density with enlarged diameters. Transplanted Bbs4-/- islets exhibit delayed re-vascularization and reduced vascular fenestration after engraftment, partially impairing vascular permeability and glucose delivery to β-cells. We identified primary cilia on endothelial cells as the underlying cause of this regulation, via the vascular endothelial growth factor-A (VEGF-A)/VEGF receptor 2 (VEGFR2) pathway. In vitro silencing of ciliary genes in endothelial cells disrupts VEGF-A/VEGFR2 internalization and downstream signaling. Consequently, key features of angiogenesis including proliferation and migration are attenuated in human BBS4 silenced endothelial cells. We conclude that endothelial cell primary cilia regulate islet vascularization and vascular barrier function via the VEGF-A/VEGFR2 signaling pathway.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Vegf-a ; Cell Biology ; Developmental Biology ; Human ; Insulin ; Islet Vascularization ; Mouse ; Pancreatic Islet ; Primary Cilia; Growth Factor-a; Pancreatic-islets; In-vivo; Transport; Cells; Revascularization; Intraflagellar; Recombination; Homeostasis; Receptors
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Journal eLife
Quellenangaben Volume: 9, Issue: , Pages: , Article Number: e56914 Supplement: ,
Publisher eLife Sciences Publications
Publishing Place Sheraton House, Castle Park, Cambridge, Cb3 0ax, England
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Regeneration Research (IDR)
POF-Topic(s) 90000 - German Center for Diabetes Research
30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-501900-233
G-502300-001
Grants European Research Council
FP7 People: Marie-Curie Actions
ERC
DOI 10.7554/eLife.56914
WOS ID WOS:000595555800001
Scopus ID 85097003065
PubMed ID 33200981
Erfassungsdatum 2020-12-17
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