Abstract:
:Neuropilin1 (Nrp1) is a co-receptor best known to regulate the development of endothelial cells and is a target of anticancer therapies. However, its role in other vascular cells including pericytes is emergent. The kidney is an organ with high pericyte density and cancer patients develop severe proteinuria following administration of NRP1B-neutralizing antibody combined with bevacizumab. Therefore, we investigated whether Nrp1 regulates glomerular capillary integrity after completion of renal development using two mouse models; tamoxifen-inducible NG2Cre to delete Nrp1 specifically in pericytes and administration of Nrp1-neutralizing antibodies. Specific Nrp1 deletion in pericytes did not affect pericyte number but mutant mice developed hematuria with glomerular basement membrane defects. Despite foot process effacement, albuminuria was absent and expression of podocyte proteins remained unchanged upon Nrp1 deletion. Additionally, these mice displayed dilation of the afferent arteriole and glomerular capillaries leading to glomerular hyperfiltration. Nidogen-1 mRNA was downregulated and collagen4α3 mRNA was upregulated with no significant effect on the expression of other basement membrane genes in the mutant mice. These features were phenocopied by treating wild-type mice with Nrp1-neutralizing antibodies. Thus, our results reveal a postdevelopmental role of Nrp1 in renal pericytes as an important regulator of glomerular basement membrane integrity. Furthermore, our study offers novel mechanistic insights into renal side effects of Nrp1 targeting cancer therapies.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Wnuk M,Anderegg MA,Graber WA,Buergy R,Fuster DG,Djonov Vdoi
10.1016/j.kint.2016.10.010subject
Has Abstractpub_date
2017-04-01 00:00:00pages
868-879issue
4eissn
0085-2538issn
1523-1755pii
S0085-2538(16)30609-3journal_volume
91pub_type
杂志文章abstract::Water and small solute fluxes through cell membranes are ensured in many tissues by selective pores that belong to the major intrinsic protein family (MIP). This family includes the water channels or aquaporins (AQP) and the neutral solute facilitators such as the glycerol facilitator (GlpF). We have compared the char...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1046/j.1523-1755.2001.060002422.x
更新日期:2001-08-01 00:00:00
abstract::The autoregulatory ability of the renal vascular system in the split hydronephrotic kidney was quantitated with intravital microscopy. The luminal diameters of the arcuate and interlobular arteries as well as the afferent and efferent arterioles were measured. Glomerular blood flow was determined by the dual slit tech...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.104
更新日期:1989-05-01 00:00:00
abstract::Pulse wave velocity (PWV) was measured in the aorta, right leg and arm of 90 control subjects (CS) and 92 hemodialysis patients (HD) of the same age and mean arterial pressure (MAP). Blood chemistry, including blood lipids, and echographic dimensions of the aorta, were measured in all subjects. Presence of aortic calc...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.19
更新日期:1990-01-01 00:00:00
abstract::Acute kidney injury (AKI) increases the risk for chronic kidney disease (CKD). However, there are few tools to detect microstructural changes after AKI. Here, cationic ferritin-enhanced magnetic resonance imaging (CFE-MRI) was applied to examine the heterogeneity of kidney pathology in the transition from AKI to CKD. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.08.021
更新日期:2021-01-01 00:00:00
abstract::In recent times, therapy for renal anemia has changed dramatically in that iron administration has increased and doses of erythropoiesis-stimulating agents (ESAs) have decreased. Here we used a prospective, observational, multicenter design and measured the serum ferritin and hemoglobin levels every 3 months for 2 yea...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1038/ki.2014.114
更新日期:2014-10-01 00:00:00
abstract::The addition of spironolactone or hydrochlorothiazide enhances the antialbuminuric effect of renin-angiotensin blockers. However, comparative studies on the effect of different diuretics are lacking. We conducted a prospective randomized crossover study to compare the effects of spironolactone (25 mg/day), hydrochloro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.249
更新日期:2015-12-01 00:00:00
abstract::The kidney clears numerous solutes from the plasma; however, retention of these solutes causes uremic illness when the kidneys fail. We know remarkably little about which retained solutes are toxic and this limits our ability to improve dialysis therapies. To explore this, we employed untargeted mass spectrometry to i...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.154
更新日期:2013-09-01 00:00:00
abstract::Glutamine accumulation in rat kidney was investigated by giving large loads of gluta, mate and aspartate and measuring glutamine changes in seven completely defined portions of the nephron and in small patches from the thin limb area and from the papilla. Both glutamate and aspartate (which is partly coverted to gluta...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1978.145
更新日期:1978-11-01 00:00:00
abstract::Bovine serum albumin (BSA, pI 4.9) was maleylated to yield highly anionic MBSA (pI 3.0). Maleylation of BSA lead to an expansion of molecular size of native BSA from an effective molecular radius (EMR) of 37 A to 57 A for MBSA as assessed by gel filtration chromatography. MBSA, but not BSA, bound to the peripheral cap...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.161
更新日期:1988-08-01 00:00:00
abstract:BACKGROUND:Carriers of autosomal-recessive and X-linked Alport syndrome often have a thinned glomerular basement membrane (GBM) and have mutations in the COL4A3/COL4A4 and COL4A5 genes respectively. Recently, we have shown that many individuals with thin basement membrane disease (TBMD) are also from families where hem...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.060002480.x
更新日期:2001-08-01 00:00:00
abstract::The candidacidal activity of kidneys, liver, and spleen's phagocytic systems was studied in mouse. Different strains of mice were inoculated intravenously (i.v.) with 1 to 2.6 x 10(4) viable Candida albicans. Elimination of the microorganisms from the kidneys, liver, and spleen were evaluated by enumeration of colony ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.225
更新日期:1991-09-01 00:00:00
abstract:UNLABELLED:Correlation of histology to rejection reversal: A Thymoglobulin Multicenter Trial report BACKGROUND:Histology may provide a link between clinical response to antirejection therapy and graft function. In a subset of centers, renal biopsy was a secondary end point for the Thymoglobulin Multicenter Trial. MET...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1046/j.1523-1755.1999.00494.x
更新日期:1999-06-01 00:00:00
abstract::Sudden death is one of the more frequent causes of death for hemodialysis patients, but the underlying mechanisms, contribution of arrhythmia, and associations with serum chemistries or the dialysis procedure are incompletely understood. To study this, implantable loop recorders were utilized for continuous cardiac rh...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2017.11.019
更新日期:2018-04-01 00:00:00
abstract:BACKGROUND:There is growing evidence pointing to an involvement of cytokines and growth factors in renal osteodystrophy. In this study, the expression of interleukin-l beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and basic fibroblast growth factor (bFGF) in bone...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00835.x
更新日期:2003-03-01 00:00:00
abstract::Simple life-table analyses have not identified the reasons for the steady improvement over the years in graft survival. The use of more sophisticated multifactorial statistical techniques is indicated to identify prognostic factors and to explore the "center effect" on graft survival. An agenda for retrospective analy...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.188
更新日期:1983-10-01 00:00:00
abstract::NO, a simple molecule synthesized from L-arginine by NO synthases, has been identified to play an important role in cell communication, cell defense and cell injury. The half life of NO is very short because NO either reacts with superoxide anion (O2-), and/or binds to heme molecules or Fe-S groups present in proteins...
journal_title:Kidney international
pub_type: 社论,评审
doi:10.1038/ki.1995.262
更新日期:1995-07-01 00:00:00
abstract::The acute renal effects of hypoxemia and the ability of theophylline to prevent these effects were assessed in anesthetized and mechanically-ventilated newborn and adult rabbits. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by the clearance of para-aminohippuric acid and inulin, respecti...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.114
更新日期:1988-06-01 00:00:00
abstract:BACKGROUND:In the United States, infection is second to cardiovascular disease as the leading cause of death in patients with end-stage renal disease (ESRD), and septicemia accounts for more than 75% of this category. This increased susceptibility to infections is partly due to uremia, old age, and comorbid conditions....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2000.00337.x
更新日期:2000-10-01 00:00:00
abstract::Intrauterine growth retardation (IUGR) aggravates the course of acute mesangioproliferative glomerulonephritis (GN) in the rat. Observational studies in children suggest that IUGR may be associated with a severe course of kidney diseases such as IgA nephropathy. We tested the hypothesis that IUGR leads to aggravation ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001966
更新日期:2006-12-01 00:00:00
abstract::Dialysis patients have a high risk of cardiovascular disease. Cardiac rehabilitation is recommended in the general population as a standard component of care and covered by Medicare for those who have undergone coronary artery bypass grafting (CABG). Here we determined the impact of cardiac rehabilitation on Medicare ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.381
更新日期:2008-10-01 00:00:00
abstract::Vascular sclerosis has been linked to many risk factors, including smoking, family history, low birth weight, and hypertension. In interesting studies, Goforth et al. show an increased rate of mutations in thrombophilic molecules in patients with vascular sclerosis in renal biopsies, suggesting yet another mechanism. ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5001721
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND:Knowledge of the long-term renal prognosis of diarrhea associated hemolytic uremic syndrome (HUS) is important for patient counseling and follow-up. However, estimates of long-term risk are highly variable, with previous studies not using a healthy control group. METHODS:A municipal water system in the smal...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00225.x
更新日期:2005-04-01 00:00:00
abstract:BACKGROUND:The inhibitor of apoptosis (IAP) family of proteins regulates programmed cell death triggered by various stimuli. The purpose of this investigation was to examine the expression, regulation, and function of IAP genes in cultured rat mesangial cells. METHODS:Basal and inducible expression of c-IAP1, c-IAP2, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.060002579.x
更新日期:2001-08-01 00:00:00
abstract::Since the kidney medulla was reported to generate platelet activating factor (PAF), we investigated a possible effect of this agent on the reabsorptive function of in vitro microperfused medullary thick ascending limbs from mouse kidney (mTAL). PAF, 10(-7) M in the bath, significantly decreased the net chloride flux (...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.38
更新日期:1992-02-01 00:00:00
abstract:BACKGROUND:Studies in animal models have shown that the alternative pathway of complement is activated in the kidney after ischemia/reperfusion. In addition, mice deficient in complement factor B, a necessary component of the alternative pathway, are protected from ischemic acute renal failure. The purpose of this stud...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.67109.x
更新日期:2005-02-01 00:00:00
abstract::Membranous nephropathy is a major cause of nephrotic syndrome in adults where podocyte injuries were found to mediate the development of proteinuria. Triptolide, a major active component of Tripterygium wilfordii Hook F, has potent immunosuppressive, anti-inflammatory and antiproteinuric effects. To study its antiprot...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.41
更新日期:2010-06-01 00:00:00
abstract::Patients receiving cadaveric kidney transplants often experience delayed graft function. As iodinated contrast media injection (ICMI), necessary for cerebral angiography, which is often used to diagnose brain death, can be nephrotoxic, we compared renal function recovery (RFR) and 1-year and long-term graft survival a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001727
更新日期:2006-09-01 00:00:00
abstract::A high frequency (25%) of anti-hepatitis C virus (HCV) antibodies is observed in French hemodialyzed patients; this is associated with detectable viremia in 85% and results in chronic hepatitis in more than 90%. We conducted a pilot study to examine the tolerance and efficacy of alpha-2b Interferon therapy upon HCV in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.198
更新日期:1995-05-01 00:00:00
abstract::The ankyrin repeat and sterile α motif (SAM) domain-containing six gene (Anks6) is a candidate for polycystic kidney disease (PKD). Originally identified in the PKD/Mhm(cy/+) rat model of PKD, the disease is caused by a mutation (R823W) in the SAM domain of the encoded protein. Recent studies support the etiological r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.122
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:Controversy exists regarding the possible associations between a single nucleotide polymorphism of the transcobalamin II encoding gene (TCN2 776C>G) and plasma levels of vitamin B(12), folate, or total homocysteine. METHODS:In a cross-sectional study of 732 kidney allograft recipients, patients were categor...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00592.x
更新日期:2004-05-01 00:00:00