Inverse correlation between vascular endothelial growth factor back-filtration and capillary filtration pressures

Kuppe, Christoph; Rohlfs, Wilko; Grepl, Martin; Schulte, Kevin; Verón, Delma; Elger, Marlies; Sanden, Silja K.; Andræ, Johanna; Betsholtz, Christer; Hausmann, Ralf; Quaggin, Susan E.; Bachmann, S.; Kriz, Wilhelm; Tufró, Alda; Floege, Jürgen; Moeller, Marcus J.

doi:10.1093/ndt/gfy057

Cited by 4 publications

(9 citation statements)

References 51 publications

(78 reference statements)

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“…These PECs displace the remaining Pods and deposit their extracellular matrix onto the glomerular basement membrane. As Pods disappear, vascular endothelial growth factor (VEGF) no longer reaches the glomerular capillaries, resulting in capillary loss ( 66 ). Ultimately, a segmental scar devoid of Pods or capillaries forms, which is the hallmark lesion in FSGS.…”

Section: Repair and Modulation Of Kidney Fibrosismentioning

confidence: 99%

New Aspects of Kidney Fibrosis–From Mechanisms of Injury to Modulation of Disease

et al. 2022

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Organ fibrogenesis is characterized by a common pathophysiological final pathway independent of the underlying progressive disease of the respective organ. This makes it particularly suitable as a therapeutic target. The Transregional Collaborative Research Center “Organ Fibrosis: From Mechanisms of Injury to Modulation of Disease” (referred to as SFB/TRR57) was hosted from 2009 to 2021 by the Medical Faculties of RWTH Aachen University and the University of Bonn. This consortium had the ultimate goal of discovering new common but also different fibrosis pathways in the liver and kidneys. It finally successfully identified new mechanisms and established novel therapeutic approaches to interfere with hepatic and renal fibrosis. This review covers the consortium's key kidney-related findings, where three overarching questions were addressed: (i) What are new relevant mechanisms and signaling pathways triggering renal fibrosis? (ii) What are new immunological mechanisms, cells and molecules that contribute to renal fibrosis?, and finally (iii) How can renal fibrosis be modulated?

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Section: Repair and Modulation Of Kidney Fibrosismentioning

confidence: 99%

New Aspects of Kidney Fibrosis–From Mechanisms of Injury to Modulation of Disease

et al. 2022

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“…Vascular endothelial growth factor (VEGF), located on chromosome 6 (6p21.1) and a key regulator of vascular formation, is initially characterized by its actions on the endothelial fenestration and maintains permeability of capillary vessels, inducing vasculogenesis, angiogenesis [ 1 , 2 ]. VEGF, an essential growth factor, is involved in the glomerular development and the postnatal homeostasis, and it is secreted by podocytes into the primary urine in high amounts, back-filtered across the glomerular capillary wall to act on the endothelial cells [ 3 ]. VEGF can repair interstitial tubule compartment in the cyclosporine nephrotoxicity, but the mRNA level of VEGF has been up-regulated in the tubules in hypoxic states [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Meta-analysis of associations of vascular endothelial growth factor protein levels and -634G/C polymorphism with systemic lupus erythematosus susceptibility

et al. 2019

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BackgroundThe purpose of this study was to detect the effects of vascular endothelial growth factor (VEGF) on systemic lupus erythematosus (SLE) risk.MethodsAssociated studies were extracted from the China Biological Medicine Database (CBM), and PubMed on June 10, 2018, and applicable investigations were pooled and analyzed by meta-analysis using RevMan 5.3.ResultsVEGF levels was associated with SLE risk (mean differences (MD) =196.02, 95% CI: 135.29–256.75, P < 0.00001), and VEGF levels was associated with active SLE risk (MD =77.51, 95% CI: 10.98–144.05, P = 0.02). We also found that VEGF levels was associated with SLE developing into lupus nephritis (LN) risk (MD =223.16, 95% CI: 144.38–301.93, P < 0.00001). However, VEGF -634G/C gene polymorphism (rs2010963) was not associated with SLE risk.ConclusionsVEGF levels was associated with SLE risk, active SLE risk and SLE developing into LN risk. However, there was no an association between VEGF -634G/C gene polymorphism and SLE risk.

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“…Using a model of VEGF transport against glomerular filtration flow, it has been calculated that about one-third of podocyte-derived VEGF-A reaches the glomerular endothelial cells via diffusion [ 13 ]. Moreover, the recent study has provided evidence of unexpected positive correlation between single-nephron glomerular filtration rate with VEGF-A back diffusion [ 14 ]. Taking into account that suramin enhances the urinary excretion of VEGF-A by 60–70% in diabetic rats, one may expect that local concentration in the glomerulus may by increased by about 20%.…”

Section: Discussionmentioning

confidence: 99%

“…VEGF-A is produced in glomeruli by podocytes and diffuses towards capillary lumens, where it reaches the glomerular endothelial cells and causes an increase in glomerular permeability to water [ 12 , 13 ]. The genetic-based study has provided evidence that increased local renal VEGF levels affect the glomerular endothelium fenestration, which is a surrogate marker for local VEGF-A bioactivity [ 14 ]. Importantly, elevated VEGF-A levels are associated with glomerular pathologies in diabetic nephropathy [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Suramin enhances the urinary excretion of VEGF-A in normoglycemic and streptozotocin-induced diabetic rats

et al. 2021

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Background Vascular endothelial growth factor A (VEGF-A) and P2-receptors (P2Rs) are involved in the pathogenesis of diabetic nephropathy. The processing of VEGF-A by matrix metalloproteinases (MMP) regulates its bioavailability. Since the ATP-induced release of MMP-9 is mediated by P2Rs, we investigated the effect of suramin on VEGF-A excretion in urine and the urinary activity of total MMP and MMP-9. Methods The effect of suramin (10 mg/kg, ip) on VEGF-A concentration in serum and its excretion in urine was investigated in streptozotocin (STZ)-induced diabetic rats over a 21-day period. The rats received suramin 7 and 14 days after a single STZ injection (65 mg/kg, ip). A 24-h collection of urine was performed on the day preceding the administration of STZ and the first administration of suramin and on the day before the end of the experiment. The VEGF-A in serum and urine, albumin in urine, and total activity of MMP and MMP-9 in urine were measured using immunoassays. Results Diabetic rats are characterized by a sixfold higher urinary excretion of VEGF-A. Suramin potentiates VEGF-A urinary excretion by 36% (p = 0.046) in non-diabetic and by 75% (p = 0.0322) in diabetic rats but it did not affect VEGF-A concentration in the serum of non-diabetic and diabetic rats. Urinary albumin excretion as well as total MMP and MMP-9 activity was increased in diabetic rats, but these parameters were not affected by suramin. Conclusion Suramin increases the urinary excretion of VEGF-A in normoglycemia and hyperglycaemia, possibly without the involvement of MMP-9. Suramin may be used as a pharmacological tool enhancing VEGF-A urinary secretion.

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Inverse correlation between vascular endothelial growth factor back-filtration and capillary filtration pressures

Abstract: Our results suggest that an additional force drives VEGF back-filtration, potentially regulated by SNGFR.

Cited by 4 publications

References 51 publications

New Aspects of Kidney Fibrosis–From Mechanisms of Injury to Modulation of Disease

New Aspects of Kidney Fibrosis–From Mechanisms of Injury to Modulation of Disease

Meta-analysis of associations of vascular endothelial growth factor protein levels and -634G/C polymorphism with systemic lupus erythematosus susceptibility

Suramin enhances the urinary excretion of VEGF-A in normoglycemic and streptozotocin-induced diabetic rats

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