Abstract：
:Aminopeptidase A is one of the most potent enzymes within the renin-angiotensin system in terms of angiotensin II degradation. Here, we examined whether there is a kidney phenotype and any compensatory changes in other renin angiotensin system enzymes involved in the metabolism of angiotensin II associated with aminopeptidase A deficiency. Kidneys harvested from aminopeptidase A knockout mice were examined by light and electron microscopy, immunohistochemistry and immunofluorescence. Kidney angiotensin II levels and the ability of renin angiotensin system enzymes in the glomerulus to degrade angiotensin II ex vivo, their activities, protein and mRNA levels in kidney lysates were evaluated. Knockout mice had increased blood pressure and mild glomerular mesangial expansion without significant albuminuria. By electron microscopy, knockout mice exhibited a mild increase of the mesangial matrix, moderate thickening of the glomerular basement membrane but a striking appearance of knob-like structures. These knobs were seen in both male and female mice and persisted after the treatment of hypertension. In isolated glomeruli from knockout mice, the level of angiotensin II was more than three-fold higher as compared to wild type control mice. In kidney lysates from knockout mice angiotensin converting enzyme activity, protein and mRNA levels were markedly decreased possibly as a compensatory mechanism to reduce angiotensin II formation. Thus, our findings support a role for aminopeptidase A in the maintenance of glomerular structure and intra-kidney homeostasis of angiotensin peptides.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Marahrens B,Schulze A,Wysocki J,Lin MH,Ye M,Kanwar YS,Bader M,Velez JCQ,Miner JH,Batlle Ddoi
10.1016/j.kint.2020.11.012subject
Has Abstractpub_date
2020-12-11 00:00:00eissn
0085-2538issn
1523-1755pii
S0085-2538(20)31420-4pub_type
杂志文章abstract：BACKGROUND:Chronic cyclosporine (CsA) nephrotoxicity is characterized by interstitial fibrosis and afferent arteriolar hyalinosis. L-arginine (L-Arg), the substrate for nitric oxide (NO) synthase and N-nitro-L-arginine-methyl ester (L-NAME), the NO synthase inhibitor, were shown to modulate acute CsA nephrotoxicity. Ho...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2000.00273.x
更新日期：2000-09-01 00:00:00
abstract：:Many approaches to blocking profibrotic TGFbeta overexpression are under way. Therapeutic targeting of TGFbeta-Smad signaling holds promise for slowing or halting progressive renal disease. In this issue, Fukasawa et al., using the unilateral ureteral obstruction model, provide a new target for therapeutic interventio...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1038/sj.ki.5000260
更新日期：2006-05-01 00:00:00
abstract：:We studied the adaptation to early (72 hr) and late (20 days) K loading (400 mmol/day, 4 equal meals every 6 hour) in six healthy humans. Throughout the study, each single K meal was followed by an acute transient rise in plasma K, aldosterone and kaliuresis. "K balance" (urinary K excretion approximately 80% of intak...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1990.295
更新日期：1990-11-01 00:00:00
abstract：:Normal urine contains thousands of proteins, largely due to the presence of 'exosomes,' tiny vesicles secreted into the urine by renal epithelial cells. These exosomes, demonstrated by Keller and colleagues to be also retrievable from amniotic fluid, offer great promise for future disease biomarker discovery studies. ...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1038/sj.ki.5002510
更新日期：2007-11-01 00:00:00
abstract：:In his hypothesis of the evolution of renal functions Homer Smith proposed that the formation of glomerular nephron and body armor had been adequate for the appearance of primitive vertebrates in fresh water and that the adaptation of homoiotherms to terrestrial life was accompanied by the appearance of the loop of He...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1038/ki.1996.220
更新日期：1996-06-01 00:00:00
abstract：:The possibility that hypercalciuria could cause calcium stone formation through a mechanism other than by increasing urinary saturation of stone-forming calcium salts was explored. The effect of increasing calcium concentration on the inhibitor activity against the spontaneous precipitation of calcium oxalate was exam...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1988.100
更新日期：1988-05-01 00:00:00
abstract：:Intercellular adhesion molecule-1 (ICAM-1) and MHC class II (Ia) antigens are increased on proximal tubular epithelial cells (TEC) in autoimmune nephritis and transplant rejection. ICAM-1 is a member of the immunoglobulin gene superfamily that increases the avidity of T cell interactions with antigen-presenting cells ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1990.221
更新日期：1990-09-01 00:00:00
abstract：:The interaction of 15-hydroxyeicosatetraenoic acid (15-HETE) and cultured MDCK renal tubular epithelial cells was investigated to determine whether incorporation of this lipoxygenase product will affect polyphosphoinositide formation. MDCK cells were incubated with 1 microM [3H]-15-HETE for 15 to 120 minutes. Maximum ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1994.131
更新日期：1994-04-01 00:00:00
abstract：:Most epidemiologic data, thus far, have focused on short-term outcomes of acute kidney injury (AKI). Lo et al. correlate AKI with long-term outcomes. The concept of 'uremic memory' sheds light on the importance of AKI and its permanent imprint. The focus of research should be on prevention of an episode of AKI, when p...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1038/ki.2009.314
更新日期：2009-10-01 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：:Tremendous progress has been made over recent years in the understanding of the mechanisms regulating calcium, phosphorus, vitamin D, and parathyroid hormone homeostasis in the normal human body and in patients with different degrees of renal failure. In addition, some of these findings have been translated into clini...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2008.692
更新日期：2009-05-01 00:00:00
abstract：BACKGROUND:Wegener's granulomatosis (WG) is a rare systemic autoimmune disease characterized by small-vessel vasculitis leading to organ damage and the presence of antineutrophil cytoplasmic autoantibodies (ANCAs). ANCAs were shown to be involved in the pathogenesis of the disease by increasing adhesion of polymorphonu...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2000.00430.x
更新日期：2000-12-01 00:00:00
abstract：:The clinical utility of cisplatin is limited by nephrotoxicity. Oh et al. report that β-lapachone prevents this nephrotoxicity but not cisplatin's cytotoxicity for cancers. In addition to its potential clinical importance, the beneficial effect of β-lapachone on cisplatin acute kidney injury may illustrate fundamental...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1038/ki.2013.419
更新日期：2014-03-01 00:00:00
abstract：:Clinical trials and experimental studies have highlighted the importance of epigenetic processes in the development of diabetic complications. One of the earliest features of diabetic nephropathy is renal enlargement. The epidermal growth factor (EGF) has a pivotal role in the development of diabetic nephromegaly and ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2011.39
更新日期：2011-06-01 00:00:00
abstract：:Crim1 is a cell-surface, transmembrane protein that binds to a variety of cystine knot-containing growth factors, including vascular endothelial growth factor A. In the developing renal glomerulus, Crim1 acts to tether vascular endothelial growth factor A to the podocyte cell surface, thus regulating its release to gl...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2009.345
更新日期：2009-12-01 00:00:00
abstract：:The soluble urokinase receptor (suPAR) promotes proteinuria and induces focal segmental glomerulosclerosis (FSGS)-like lesions in mice. A serum suPAR concentration cutoff of 3000 pg/ml has been proposed as a clinical biomarker for patients with FSGS. Interestingly, several studies in patients with glomerulopathy found...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2013.505
更新日期：2014-03-01 00:00:00
abstract：:Substantial evidence implicates impaired renal excretion of sodium as the major culprit in the pathogenesis of hypertension. The key question is: How does the impairment of Na+ excretion lead to increased peripheral vascular resistance and elevation of the blood pressure? Here we describe the evidence that elevated le...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1038/ki.1996.260
更新日期：1996-06-01 00:00:00
abstract：:In summary, it is evident that malnutrition is highly prevalent in ESRD patients. This is clearly related to multiple factors encountered during the pre-dialysis stage, as well as during maintenance dialysis therapy. A body of evidence highlights the existence of relationship between malnutrition and outcome in this p...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1038/ki.1996.323
更新日期：1996-08-01 00:00:00
abstract：:Dysregulated production of adipocytokines may be involved in the development of atherosclerotic cardiovascular disease in metabolic syndrome and chronic kidney disease (CKD) associated with metabolic syndrome. The aim of this study was to determine the effects of treatment with angiotensin II (Ang II) type-1 receptor ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/sj.ki.5001810
更新日期：2006-11-01 00:00:00
abstract：INTRODUCTION:Thiazide diuretics have the unique characteristic of increasing renal Na+ excretion, while decreasing Ca2+ excretion. However, the molecular mechanism responsible for this thiazide-induced hypocalciuria remains unclear. The present study investigates the effect of thiazides on the expression of the protein...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2003.00128.x
更新日期：2003-08-01 00:00:00
abstract：:Acute kidney injury (AKI) severe enough to require dialysis is increasing and associated with high mortality, yet robust information about temporal epidemiology of AKI requiring dialysis in England is lacking. In this retrospective observational study of the Hospital Episode Statistics (HES) data set covering the enti...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2015.234
更新日期：2015-11-01 00:00:00
abstract：BACKGROUND:Non-(1-84) parathyroid hormone (PTH) fragments are large circulating carboxyl-terminal (C) fragments with a partially preserved amino-terminal (N) structure. hPTH (7-84), a synthetic surrogate, has been demonstrated to exert biologic effects in vivo and in vitro which are opposite to those of hPTH (1-34) on ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1111/j.1523-1755.2005.00493.x
更新日期：2005-09-01 00:00:00
abstract：:A second generation hepatitis C virus recombinant immunoblot assay (RIBA) was used to screen stored perioperative serum from 641 renal allograft recipients. One hundred and nine (17%) were anti-HCV positive at the time of transplant. RIBA positivity was found to be an independent predictor of post-transplant liver dis...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1994.29
更新日期：1994-01-01 00:00:00
abstract：:The possibility that the rabbit collecting tubule is heterogeneous with respect to electrical and morphologic properties was examined in isolated segments. Collecting tubules from rabbits treated with desoxycorticosterone acetate were dissected from various locations within the cortex and outer medulla, and the transe...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1978.167
更新日期：1978-12-01 00:00:00
abstract：BACKGROUND:Podocytes play an important role in the development of proteinuria and focal glomerulosclerosis. Previously we have demonstrated that a combination of two monoclonal antibodies (mAb) against aminopeptidase A (APA), an enzyme present on podocytes, induces a massive acute albuminuria in mice. The present study...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2002.00428.x
更新日期：2002-07-01 00:00:00
abstract：:Pathological classifications in current use for the assessment of glomerular disease have been typically opinion-based and built on the expert assumptions of renal pathologists about lesions historically thought to be relevant to prognosis. Here we develop a unique approach for the pathological classification of a glo...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2009.168
更新日期：2009-09-01 00:00:00
abstract：:Despite the high costs of treatment of people with kidney disease and associated comorbid conditions, the amount of reliable information available to guide the care of such patients is very limited. Some treatments have been assessed in randomized trials, but most such trials have been too small to detect treatment ef...
journal_title：Kidney international
pub_type：
doi：10.1016/j.kint.2017.04.019
更新日期：2017-08-01 00:00:00
abstract：:Using in situ hybridization and immunocytochemistry we describe the renal localization of the PDGF alpha-receptor. PDGF alpha-receptor mRNA was uniformly present in human metanephric kidney in interstitial cells and vascular arcades that course through the blastema. PDGF alpha-receptor mRNA was present in some mesangi...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1997.157
更新日期：1997-04-01 00:00:00
abstract：:Fifty-one adults with HIV infection, including 20 chronic hemodialysis patients with superimposed HIV infection and 31 patients with HIV-associated nephropathy requiring chronic maintenance hemodialysis were followed to evaluate survival on outpatient dialysis in relation to the clinical stage of the HIV infection. Re...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1988.172
更新日期：1988-08-01 00:00:00
abstract：:Previous studies have shown that nonsteroidal anti-inflammatory drug (NSAID) use might be associated with a lower risk of developing cancer in the general population. Patients on dialysis have increased risk for cancer, but there are no studies to determine the relationship between NSAID use and cancer risk in these p...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2013.79
更新日期：2013-07-01 00:00:00
