Articles by Megan Stevens in JoVE
Assessment of Kidney Function in Mouse Models of Glomerular Disease Megan Stevens1,2,3, Sebastian Oltean1,2,3 1Institute of Biomedical and Clinical Sciences, Medical School, University of Exeter, 2School of Physiology, Pharmacology and Neurosciences, University of Bristol, 3Bristol Renal, School of Clinical Sciences, University of Bristol This protocol describes a full kidney work-up that should be carried out in mouse models of glomerular disease. The methods allow for detailed functional, structural, and mechanistic analysis of glomerular function, which can be applied to all mouse models of glomerular disease.
Other articles by Megan Stevens on PubMed
VEGF-A B Protects Against Proteinuria in a Mouse Model with Progressive Depletion of All Endogenous VEGF-A Splice Isoforms from the Kidney The Journal of Physiology. Oct, 2017 | Pubmed ID: 28574576 Progressive depletion of all vascular endothelial growth factor A (VEGF-A) splice isoforms from the kidney results in proteinuria and increased glomerular water permeability, which are both rescued by over-expression of VEGF-A b only. VEGF-A b rescues the increase in glomerular basement membrane and podocyte slit width, as well as the decrease in sub-podocyte space coverage, produced by VEGF-A depletion. VEGF-A b restores the expression of platelet endothelial cell adhesion molecule in glomerular endothelial cells and glomerular capillary circumference. VEGF-A b has opposite effects to VEGF-A on the expression of genes involved in endothelial cell migration and proliferation.
Vascular Endothelial Growth Factor-A165b Restores Normal Glomerular Water Permeability in a Diphtheria-Toxin Mouse Model of Glomerular Injury Nephron. 2018 | Pubmed ID: 29393270 Genetic cell ablation using the human diphtheria toxin receptor (hDTR) is a new strategy used for analysing cellular function. Diphtheria toxin (DT) is a cytotoxic protein that leaves mouse cells relatively unaffected, but upon binding to hDTR it ultimately leads to cell death. We used a podocyte-specific hDTR expressing (Pod-DTR) mouse to assess the anti-permeability and cyto-protective effects of the splice isoform vascular endothelial growth factor (VEGF-A165b).
Modulation of VEGF-A Alternative Splicing As a Novel Treatment in Chronic Kidney Disease Genes. Feb, 2018 | Pubmed ID: 29462869 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-Ab, known to have anti-angiogenic and anti-permeability properties. Dysregulation of the VEGF-A/VEGF-Ab 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-Ab 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.