Modulation of VEGF-A Alternative Splicing as a Novel Treatment in Chronic Kidney Disease
AbstractVascular 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
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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.
Stevens M, Oltean S. Modulation of VEGF-A Alternative Splicing as a Novel Treatment in Chronic Kidney Disease. Genes. 2018; 9(2):98.Chicago/Turabian Style
Stevens, Megan; Oltean, Sebastian. 2018. "Modulation of VEGF-A Alternative Splicing as a Novel Treatment in Chronic Kidney Disease." Genes 9, no. 2: 98.