Sebastian Oltean
Vascular endothelial growth factor-A165b is protective and restores endothelial glycocalyx in diabetic nephropathy
Oltean, Sebastian; Qiu, Yan; Ferguson, Joanne K.; Stevens, Megan; Neal, Chris; Russell, Amy; Kaura, Amit; Arkill, Kenton P.; Harris, Kirstie; Symonds, Clare; Lacey, Katja; Wijeyaratne, Lihini; Gammons, Melissa; Wylie, Emma; Hulse, Richard P.; Alsop, Chloe; Cope, George; Damodaran, Gopinath; Betteridge, Kai B.; Ramnath, Raina; Satchell, Simon C.; Foster, Rebecca R.; Ballmer-Hofer, Kurt; Donaldson, Lucy F.; Barratt, Jonathan; Baelde, Hans J.; Harper, Steven J.; Bates, David O.; Salmon, Andrew H.J.
Authors
Yan Qiu
Joanne K. Ferguson
Megan Stevens
Chris Neal
Amy Russell
Amit Kaura
KENTON ARKILL Kenton.Arkill@nottingham.ac.uk
Associate Professor
Kirstie Harris
Clare Symonds
Katja Lacey
Lihini Wijeyaratne
Melissa Gammons
Emma Wylie
Richard P. Hulse
Chloe Alsop
George Cope
Gopinath Damodaran
Kai B. Betteridge
Raina Ramnath
Simon C. Satchell
Rebecca R. Foster
Kurt Ballmer-Hofer
Lucy F. Donaldson
Jonathan Barratt
Hans J. Baelde
Steven J. Harper
DAVID BATES David.Bates@nottingham.ac.uk
Professor of Oncology
Andrew H.J. Salmon
Abstract
Diabetic nephropathy is the leading cause of ESRD in high-income countries and a growing problem across the world. Vascular endothelial growth factor-A (VEGF-A) is thought to be a critical mediator of vascular dysfunction in diabetic nephropathy, yet VEGF-A knockout and overexpression of angiogenic VEGF-A isoforms each worsen diabetic nephropathy. We examined the vasculoprotective effects of the VEGF-A isoform VEGF-A165b in diabetic nephropathy. Renal expression of VEGF-A165b mRNA was upregulated in diabetic individuals with well preserved kidney function, but not in those with progressive disease. Reproducing this VEGF-A165b upregulation in mouse podocytes in vivo prevented functional and histologic abnormalities in diabetic nephropathy. Biweekly systemic injections of recombinant human VEGF-A165b reduced features of diabetic nephropathy when initiated during early or advanced nephropathy in a model of type 1 diabetes and when initiated during early nephropathy in a model of type 2 diabetes. VEGF-A165b normalized glomerular permeability through phosphorylation of VEGF receptor 2 in glomerular endothelial cells, and reversed diabetes-induced damage to the glomerular endothelial glycocalyx. VEGF-A165b also improved the permeability function of isolated diabetic human glomeruli. These results show that VEGF-A165b acts via the endothelium to protect blood vessels and ameliorate diabetic nephropathy.
Journal Article Type | Article |
---|---|
Acceptance Date | Oct 15, 2014 |
Publication Date | Aug 1, 2015 |
Deposit Date | Aug 28, 2018 |
Print ISSN | 1046-6673 |
Electronic ISSN | 1533-3450 |
Publisher | American Society of Nephrology |
Peer Reviewed | Peer Reviewed |
Volume | 26 |
Issue | 8 |
DOI | https://doi.org/10.1681/ASN.2014040350 |
Public URL | https://nottingham-repository.worktribe.com/output/1104781 |
Publisher URL | https://jasn.asnjournals.org/content/26/8/1889 |
PMID | 25542969 |
Additional Information | eStaffProfile Description: , eStaffProfile Brief Description of Type: |
You might also like
Targeting FGFRs Using PD173074 as a Novel Therapeutic Strategy in Cholangiocarcinoma
(2023)
Journal Article
Looking Under the Lamppost: The Search for New Cancer Targets in the Human Kinome
(2022)
Journal Article
Non?invasive measurement of retinal permeability in a diabetic rat model
(2020)
Journal Article
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: discovery-access-systems@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search