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

ELife
Yan XiongPer-Olof Berggren

Abstract

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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Citations

Jan 12, 2021·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Salamah M AlwahshShareen Forbes
Mar 31, 2021·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Andrew R Pepper, Gregory S Korbutt
May 11, 2021·Frontiers in Endocrinology·Erwin Ilegems, Per-Olof Berggren
May 14, 2021·Frontiers in Endocrinology·Guzel BurganovaLimor Landsman

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Datasets Mentioned

BETA
AB5320

Methods Mentioned

BETA
imaging techniques
transgenic
targeted knockout
confocal microscopy
Assay
ELISA
transfection
Protein Assay
PCR

Software Mentioned

Time Series Analyzer
QuantStudio 5
Image Lab
GraphPad Prism
Volocity
MATLAB
Fiji

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