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Genes 2018, 9(2), 98;

Modulation of VEGF-A Alternative Splicing as a Novel Treatment in Chronic Kidney Disease

Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, EX1 2LU, UK
Authors to whom correspondence should be addressed.
Received: 2 December 2017 / Revised: 8 February 2018 / Accepted: 9 February 2018 / Published: 15 February 2018
(This article belongs to the Special Issue Aberrant Pre-mRNA Splicing in Disease)
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Vascular endothelial growth factor A (VEGF-A) is a prominent pro-angiogenic and pro-permeability factor in the kidney. Alternative splicing of the terminal exon of VEGF-A through the use of an alternative 3′ splice site gives rise to a functionally different family of isoforms, termed VEGF-Axxxb, known to have anti-angiogenic and anti-permeability properties. Dysregulation of the VEGF-Axxx/VEGF-Axxxb isoform balance has recently been reported in several kidney pathologies, including diabetic nephropathy (DN) and Denys–Drash syndrome. Using mouse models of kidney disease where the VEGF-A isoform balance is disrupted, several reports have shown that VEGF-A165b treatment/over-expression in the kidney is therapeutically beneficial. Furthermore, inhibition of certain splice factor kinases involved in the regulation of VEGF-A terminal exon splicing has provided some mechanistic insight into how VEGF-A splicing could be regulated in the kidney. This review highlights the importance of further investigation into the novel area of VEGF-A splicing in chronic kidney disease pathogenesis and how future studies may allow for the development of splicing-modifying therapeutic drugs. View Full-Text
Keywords: VEGF-A; alternative splicing; kidney disease VEGF-A; alternative splicing; kidney disease

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Stevens, M.; Oltean, S. Modulation of VEGF-A Alternative Splicing as a Novel Treatment in Chronic Kidney Disease. Genes 2018, 9, 98.

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