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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)

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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

Corresponding Author

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

ISSN (print) / ISBN 2050-084X

e-ISSN 2050-084X

Journal eLife

Quellenangaben Volume: 9, Article Number: e56914

Publisher eLife Sciences Publications

Publishing Place Sheraton House, Castle Park, Cambridge, Cb3 0ax, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Regeneration Research (IDR)

Grants European Research Council
FP7 People: Marie-Curie Actions
ERC