Journal
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 26, Issue 8, Pages 1889-1904Publisher
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2014040350
Keywords
-
Categories
Funding
- Medical Research Council [G0802829, G10002073, GR0600920]
- Kidney Research UK [RP18/2010, RP45/2013, ST5/2012]
- British Heart Foundation [FS/05/114/19959, FS/10/017/28249, PG08/022/21636, PG/08/059/25335]
- Wellcome Trust [079736]
- Diabetes UK [RJ5522]
- BBSRC [BB//J007293/1]
- Swiss National Science Foundation [31003A-130463]
- Oncosuisse [OC2 01200-08-2007]
- NOVARTIS Stiftung fur medizinischbiologische Forschung [10C61]
- Richard Bright VEGF Research Trust
- Biotechnology and Biological Sciences Research Council [BB/J007293/2, BB/J007293/1] Funding Source: researchfish
- British Heart Foundation [PG/12/51/29705] Funding Source: researchfish
- Diabetes UK [10/0004003, 11/0004192] Funding Source: researchfish
- Kidney Research UK [IN9/2013] Funding Source: researchfish
- Medical Research Council [G1002073, G0600920] Funding Source: researchfish
- BBSRC [BB/J007293/1, BB/J007293/2] Funding Source: UKRI
- MRC [G0802829, G1002073, G0600920] Funding Source: UKRI
Ask authors/readers for more resources
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-A(165)b in diabetic nephropathy. Renal expression of VEGF-A(165)b mRNA was upregulated in diabetic individuals with well preserved kidney function, but not in those with progressive disease. Reproducing this VEGF-A(165)b upregulation in mouse podocytes in vivo prevented functional and histologic abnormalities in diabetic nephropathy. Biweekly systemic injections of recombinant human VEGF-A(165)b 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-A(165)b normalized glomerular permeability through phosphorylation of VEGF receptor 2 in glomerular endothelial cells, and reversed diabetes-induced damage to the glomerular endothelial glycocalyx. VEGF-A(165)b also improved the permeability function of isolated diabetic human glomeruli. These results show that VEGF-A(165)b acts via the endothelium to protect blood vessels and ameliorate diabetic nephropathy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available