Abstract:
:Emerging evidence of crosstalk between glomerular cells in pathological settings provides opportunities for novel therapeutic discovery. Here we investigated underlying mechanisms of early events leading to filtration barrier defects of podocyte and glomerular endothelial cell crosstalk in the mouse models of primary podocytopathy (podocyte specific transforming growth factor-β receptor 1 signaling activation) or Adriamycin nephropathy. We found that glomerular endothelial surface layer degradation and albuminuria preceded podocyte foot process effacement. These abnormalities were prevented by endothelin receptor-A antagonism and mitochondrial reactive oxygen species scavenging. Additional studies confirmed increased heparanase and hyaluronoglucosaminidase gene expression in glomerular endothelial cells in response to podocyte-released factors and to endothelin-1. Atomic force microscopy measurements showed a significant reduction in the endothelial surface layer by endothelin-1 and podocyte-released factors, which could be prevented by endothelin receptor-A but not endothelin receptor-B antagonism. Thus, our studies provide evidence of early crosstalk between activated podocytes and glomerular endothelial cells resulting in loss of endothelial surface layer, glomerular endothelial cell injury and albuminuria. Hence, activation of endothelin-1-endothelin receptor-A and mitochondrial reactive oxygen species contribute to the pathogenesis of primary podocytopathies in experimental focal segmental glomerulosclerosis.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Ebefors K,Wiener RJ,Yu L,Azeloglu EU,Yi Z,Jia F,Zhang W,Baron MH,He JC,Haraldsson B,Daehn Idoi
10.1016/j.kint.2019.05.007subject
Has Abstractpub_date
2019-10-01 00:00:00pages
957-970issue
4eissn
0085-2538issn
1523-1755pii
S0085-2538(19)30524-1journal_volume
96pub_type
杂志文章abstract::Although it has been recognized for more than 140 years that the pacemaker driving pyeloureteric peristalsis resides within the kidney, the cellular mechanisms underlying this autorhythmicity have been little investigated. The demonstration by Hurtado et al. of a role of hyperpolarization-activated cation channels in ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2009.485
更新日期:2010-03-01 00:00:00
abstract::Although the pathogenesis of steroid-sensitive nephrotic syndrome (SSNS) remains elusive, multiple epidemiologic, clinical, and experimental studies converge on the common theme of immune dysregulation. Initially, T-cell adaptive immunity was solely emphasized; however, the role of humoral immunity in nephrotic syndro...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2019.05.031
更新日期:2019-10-01 00:00:00
abstract::Activation of cAMP signaling pathway was shown to inhibit some pathobiologic processes in mesangial cells (MC). We investigated whether adrenomedullin (ADM), a potent agonist of adenylate cyclase, is synthesized in MC and whether it can, via cAMP, suppress the generation of reactive oxygen metabolites (ROM) and prolif...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.413
更新日期:1997-10-01 00:00:00
abstract::Micropuncture studies were carried out in surface nephrons of rats with nephrotoxic-serum (NTS)-induced nephrotic syndrome during a period of active sodium and water retention. It was found that hydrostatic pressure and tubular diameter were increased in the proximal tubules (13.4 +/- 0.2 vs. 10.4 +/- 0.2 mm Hg; 31.3 ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1979.166
更新日期:1979-11-01 00:00:00
abstract::Sodium thiosulfate, a reversible oxidation product of hydrogen sulfide, has vasodilating and anti-oxidative properties, making it an attractive agent to alleviate damaging effects of hypertension. In experimental settings, inhibition of nitric oxide synthase causes hypertension, renal dysfunction and damage. We hypoth...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.02.020
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:A need exists for a therapy that lowers parathyroid hormone (PTH) without increasing calcium x phosphorus in patients with secondary hyperparathyroidism. The calcimimetic AMG 073 increases the sensitivity of the parathyroid calcium-sensing receptor to extracellular calcium, thereby reducing PTH secretion. Co...
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.1523-1755.2003.00720.x
更新日期:2003-01-01 00:00:00
abstract::The purpose of these studies was to test the hypothesis that Randall's plaque develops in unique anatomical sites of the kidney and their formation is conditioned by specific stone-forming pathophysiologies. We performed intraoperative papillary biopsies from kidneys of idiopathic-calcium oxalate (CaOx), intestinal by...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5000238
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND:Population-genetic studies investigating genetic polymorphisms of Mendelian inheritance should always test whether the measured genotype frequencies deviate from the expected one. For this purpose Hardy-Weinberg (HW) criteria are generally used. If genotype distribution of control population misses HW equili...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00596.x
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND:In a prior study the 21-aminosteroid (lazaroid) U74389F provided in vivo protection from oxidative stress when used as a preventive therapy in ischemia-reperfusion injury in the kidney. As the cell membrane is the principal site for lipoperoxidation, in the current study the very lipophilic 2-methylaminochro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00072.x
更新日期:1998-09-01 00:00:00
abstract:BACKGROUND:The measurement of many parameters of human blood is usually performed in plasma or serum. Since lipoproteins or apolipoproteins, for example, are found almost exclusively in the plasma fraction after low-speed centrifugation, these parameters can be expected to be distributed in a different plasma volume de...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00086.x
更新日期:1998-10-01 00:00:00
abstract::The role of endogenous atrial natriuretic peptide (ANP) in the immediate response of sodium excretion to unilateral nephrectomy (UNX) was investigated in anesthetized euvolemic rats through measurement of UNX-induced change in plasma ANP concentration and the response of the remaining kidney to UNX following administr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.178
更新日期:1993-06-01 00:00:00
abstract::Lipid abnormalities have been suggested as a major cause of the accelerated atherosclerosis and the high incidence of coronary heart disease in chronic renal failure patients. In the present work the postprandial lipoprotein metabolism was studied in chronic dialysis patients with or without fasting hypertriglyceridem...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.411
更新日期:1992-11-01 00:00:00
abstract::Medial arterial calcification involves chondrogenic/osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Zhao et al. report that phosphate activates the mammalian target of rapamycin (mTOR) cascade in VSMCs, leading to downregulation of Klotho. Furthermore, rapamycin was shown to halt medial calcif...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2015.223
更新日期:2015-10-01 00:00:00
abstract::Hemodynamic factors may play a role in the development of acute renal failure following administration of contrast media (CM). In this study the effect of intravenous injection of contrast media and mannitol on red blood cell velocity (VRBC) and red blood cell aggregation in renal medullary vessels was studied in 58 r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.181
更新日期:1996-05-01 00:00:00
abstract::Sodium depletion has a protective effect on target-organ damage in hypertension independent of blood pressure. Here we tested whether chronic dietary sodium restriction may prevent the development of renal alterations associated with insulin resistance by reducing the inflammatory and oxidant state. Rats were fed norm...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.478
更新日期:2013-04-01 00:00:00
abstract::Steroid Resistant Nephrotic Syndrome (SRNS) in children and young adults has differing etiologies with monogenic disease accounting for 2.9-30% in selected series. Using whole exome sequencing we sought to stratify a national population of children with SRNS into monogenic and non-monogenic forms, and further define t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.10.013
更新日期:2017-04-01 00:00:00
abstract::Dopamine plays an important role in regulation of renal sodium transport. Proximal tubule cells produce dopamine after decarboxylation of L-DOPA via the enzyme aromatic L-amino acid decarboxylase (AADC). The presence and cellular localization of AADC-like immunoreactivity (-LI) and AADC mRNA were examined during pre- ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.326
更新日期:1992-09-01 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::Although the goal glomerular filtration rate (GFR) for chronic dialysis initiation is currently above 5 ml/min per 1.73 m(2), there is no convincing evidence that patients will benefit from this approach. With close follow-up of advanced chronic kidney disease patients, aiming to start dialysis at an estimated GFR (eG...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.164
更新日期:2014-10-01 00:00:00
abstract::Epigenetic mechanisms have been the focus of intensive research. De Marinis et al. demonstrated that high glucose levels exert stimulatory effects on activation histone marks, leading to the upregulation of thioredoxin-interacting protein (TXNIP) gene expression, which is proinflammatory. They also showed that the eff...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2015.12.026
更新日期:2016-02-01 00:00:00
abstract::Progranulin (PGRN), an autocrine growth factor, has multiple physiological functions and is widely involved in the pathogenesis of many types of diseases. The pivotal anti-inflammatory function of PGRN in rheumatoid arthritis encouraged us to examine the role of PGRN in acute kidney injury (AKI). We found that levels ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.403
更新日期:2015-05-01 00:00:00
abstract::The mean renal tubular diameters, number of tubules per unit of cross-sectional area, and fraction of the total volume occupied by each medullary structure were determined at various levels of the renal medulla of the rat and rabbit. Statistical estimates of anatomic variables were made using spatial sampling techniqu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.118
更新日期:1977-11-01 00:00:00
abstract::About 75% of urinary stones contain oxalate. As Oxalobacter formigenes is a Gram-negative anaerobic bacterium that degrades oxalate in the intestinal tract, we assessed the role of O. formigenes in oxalate metabolism by evaluating its intestinal absorption, plasma concentration, and urinary excretion. Of 37 calcium ox...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.104
更新日期:2013-06-01 00:00:00
abstract::Low nephron number has been related to low birth weight and hypertension. In the southeastern United States, the estimated prevalence of chronic kidney disease due to hypertension is five times greater for African Americans than white subjects. This study investigates the relationships between total glomerular number ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000041
更新日期:2006-02-01 00:00:00
abstract::From the urine of patients with calcium nephrolithiasis, and of control subjects, we isolated organic substances according to molecular size and tested them for effects on calcium oxalate precipitation. Nine subgroup materials of varying sizes were prepared by ultrafiltration and Sephadex G-200 column chromatography f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.33
更新日期:1982-02-01 00:00:00
abstract::Renal proximal tubule cells from spontaneously hypertensive rats (SHR), compared with normotensive Wistar-Kyoto rats (WKY), have increased oxidative stress. The contribution of mitochondrial oxidative phosphorylation to the subsequent hypertensive phenotype remains unclear. We found that renal proximal tubule cells fr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.397
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:Inhibition of angiotensin action, pharmacologically or genetically, during the neonatal period leads to renal anomalies involving hypoplastic papilla and dilated calyx. Recently, we documented that angiotensinogen (Agt -/-) or angiotensin type 1 receptor nullizygotes (Agtr1 -/-) do not develop renal pelvis n...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00420.x
更新日期:1999-05-01 00:00:00
abstract::This very brief summary of the various possible contributions of PG to normal and abnormal renal function should highlight the problem of assigning a specific role to PG in overall renal physiology and pathophysiology. PG produced in specific segments of the nephron will affect specific functions occurring in this seg...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1986.13
更新日期:1986-01-01 00:00:00
abstract::How the dialysis dose is normalized is just one of several assumptions that clinicians need to take into account when prescribing peritoneal dialysis. El-Kateb et al. confirm that estimating the volume of urea distribution is associated with significant error and show that energy expenditure is not linearly related to...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.09.020
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND:The renin-angiotensin system has been known to regulate blood pressure and body fluid homeostasis. Several lines of evidence have shown that renin gene expression and release are up-regulated by beta-adrenergic stimulation, sodium depletion, and angiotensin converting enzyme inhibition, but down-regulated by...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00209.x
更新日期:1998-12-01 00:00:00