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 of PGRN were significantly reduced in the kidney in a mouse model of renal ischemia/reperfusion injury. We also observed that PGRN deficiency (Grn(-/-) mice) significantly aggravated renal injury as evidenced by higher serum creatinine, more severe morphological injury, increased tubular epithelial cell death, and tubulointerstitial neutrophil and macrophage infiltration versus wild-type mice. In vitro, we found that recombinant human PGRN attenuated hypoxia-induced inflammatory actions and apoptosis in proximal tubule epithelial cells, at least in part associated with a nucleotide-binding oligomerization domain containing 2 (NOD2)-mediated immune response. Importantly, pretreatment with or delayed administration of recombinant human PGRN protected against or promoted recovery from renal ischemia/reperfusion injury in wild-type and Grn(-/-) mice. Similar protective effects were also found in cisplatin-induced AKI. Thus, our findings provide a better understanding of the biological activities of PGRN in the kidney and suggest that PGRN may be an innovative therapeutic strategy for treating patients with AKI.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Zhou M,Tang W,Fu Y,Xu X,Wang Z,Lu Y,Liu F,Yang X,Wei X,Zhang Y,Liu J,Geng X,Zhang C,Wan Q,Li N,Yi Fdoi
10.1038/ki.2014.403subject
Has Abstractpub_date
2015-05-01 00:00:00pages
918-29issue
5eissn
0085-2538issn
1523-1755pii
S0085-2538(15)30101-0journal_volume
87pub_type
杂志文章abstract：:IgA nephropathy is the most common primary glomerulonephritis worldwide. Its frequent coexistence with inflammatory, infectious, or malignant processes raises the possibility of a pathologic rather than coincidental association. Major strides have been made to elucidate the underlying pathophysiologic events that culm...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1016/j.kint.2018.02.030
更新日期：2018-10-01 00:00:00
abstract：:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is a lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), and even less is available in patients on maintenance hemodialysis therapy than in the g...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2020.04.031
更新日期：2020-07-01 00:00:00
abstract：:Recent decades have witnessed the revelation of expanding roles of the vitamin D endocrine system beyond calcium and phosphorus metabolism. Along with these non-calcemic or non-classic actions of vitamin D are newly discovered therapeutic actions of vitamin D analogs in a number of pathological conditions, including k...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2009.175
更新日期：2010-07-01 00:00:00
abstract：:Levels of components of the classical and alternative complement pathways and the activity of the C3 nephritic factor (C3NeF) were measured in serum specimens from patients with type I (subendothelial deposits) and type II (intramembranous dense deposits) membranoproliferative glomerulonephritis (MPGN) and the results...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1976.6
更新日期：1976-01-01 00:00:00
abstract：BACKGROUND:Transplantation of developing metanephroi into adult hosts has been proposed as a means to augment host renal function. METHODS:We implanted whole metanephroi from embryonic day 15 (E15) rats subcapsularly in kidneys or into the omentum of non-immunosupressed adult rat hosts. At the time of implantation, so...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1998.00971.x
更新日期：1998-07-01 00:00:00
abstract：:The essential role of the glycoprotein hormone erythropoietin (Epo) in the control of red blood cell production is well established. Synthesis of Epo is induced in response to low oxygen (hypoxia). In response to stimulation, increases in serum Epo levels are paralleled by changes in the abundance of Epo mRNA. These c...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1997.70
更新日期：1997-02-01 00:00:00
abstract：:Recent advances have led to a greater appreciation of how mitochondrial dysfunction contributes to diverse acute and chronic pathologies. Indeed, mitochondria have received increasing attention as a therapeutic target in a variety of diseases because they serve as key regulatory hubs uniquely situated at crossroads be...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1016/j.kint.2017.05.034
更新日期：2017-11-01 00:00:00
abstract：:Cardiac surgery associated-acute kidney injury (CS-AKI) occurs in 30-50% of patients undergoing surgery for congenital heart disease. Here we determine if CS-AKI is associated with chronic kidney disease (CKD) in patients with congenital heart disease. Using Danish regional population-based registries, our cohort stud...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2017.02.021
更新日期：2017-09-01 00:00:00
abstract：:Osteonectin (SPARC, culture shock protein, BM-40) is a widely distributed glycoprotein which binds calcium and several extracellular matrix proteins, including interstitial collagens and thrombospondin, but whose physiologic role remains undefined. In the present studies, we have demonstrated that immunoreactive osteo...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1992.8
更新日期：1992-01-01 00:00:00
abstract：:The involvement of sodium/potassium-ATPase in regulating parathyroid hormone (PTH) secretion is inferred from in vitro studies. Recently, the α-klotho-dependent rapid recruitment of this ATPase to the parathyroid cell plasma membrane in response to low extracellular calcium ion was suggested to be linked to increased ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2010.501
更新日期：2011-04-01 00:00:00
abstract：:We examined the potential of in vivo linkage of plasminogen activator inhibitor-1 (PAI-1) and angiotensin II (Ang II) in the setting of endothelial injury and sclerosis following radiation injury in the rat. PAI-1 is a major physiological inhibitor of the plasminogen activator (PA)/plasmin system, a key regulator of f...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1997.20
更新日期：1997-01-01 00:00:00
abstract：BACKGROUND:The cardiovascular effects of angiotensin II are mediated by the angiotensin II type 1 receptor (AGT1R); one polymorphism of the AGT1R gene, A1166-->C, has been associated with hypertension. The hemodynamic response to angiotensin II is blunted in women compared to men, but interactions between gender, blood...
journal_title：Kidney international
pub_type： 临床试验,杂志文章
doi：10.1046/j.1523-1755.2003.00867.x
更新日期：2003-04-01 00:00:00
abstract：:It has been proposed that one of the primary events in the development of essential hypertension is a growth-related process initiated as early as during fetal development. Differences in kidney size have been observed between most rat models of hypertension and their respective controls. In this study, we analyzed re...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1998.00938.x
更新日期：1998-06-01 00:00:00
abstract：BACKGROUND:We hypothesized that increasing small solute clearance in peritoneal dialysis (PD) would lead to improvements in patient health-related quality of life (HRQOL). METHODS:Patients were randomized to a control group [standard 4 x 2 L continuous ambulatory peritoneal dialysis (CAPD)] and an intervention group (...
journal_title：Kidney international
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1523-1755.2005.00175.x
更新日期：2005-03-01 00:00:00
abstract：:Large epidemiological studies clearly demonstrate that multiple episodes of acute kidney injury contribute to the development and progression of kidney fibrosis. Although our understanding of kidney fibrosis has improved in the past two decades, we have limited therapeutic strategies to halt its progression. Myofibrob...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2017.03.037
更新日期：2017-11-01 00:00:00
abstract：BACKGROUND:The induction of stress response (heat shock) proteins (HSPs) is a highly conserved response that protects many cell types from diverse physiological and environmental stressors. We tested the hypothesis that the induction of HSPs is protective in experimental renal ischemia/reperfusion injury. METHODS:The ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2001.0590051798.x
更新日期：2001-05-01 00:00:00
abstract：:Continuous antigen stimulation during chronic infection or malignancy can promote functional T cell silencing, a phenomenon called T cell exhaustion. The prevalence and impact of T cell exhaustion following organ transplantation, another immune stimulus with persistently high antigen load, are unknown. Here, we charac...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2019.01.040
更新日期：2019-08-01 00:00:00
abstract：BACKGROUND:Genetic polymorphisms of the angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) genes are associated with increased risk of hypertension and left ventricular hypertrophy (LVH) in hypertensive subjects. However, the extent to which these polymorphisms are related to LVH and remodeling in dialysis p...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2003.00933.x
更新日期：2003-05-01 00:00:00
abstract：BACKGROUND:Clinical studies have shown that the angiotensin-converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor antagonists decrease proteinuria and slow the progression of nephropathy in diabetes, indicating that Ang II plays an important role in the development of nephropathy. We have previously re...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1999.00271.x
更新日期：1999-02-01 00:00:00
abstract：:The profibrotic adhesion molecule, osteopontin (OPN), is upregulated in kidneys of humans and mice with diabetes. The thiazolidinedione (TZD) insulin sensitizers decrease albuminuria in diabetic nephropathy (DN) and reduce OPN expression in vascular and cardiac tissue. To examine whether OPN is a critical mediator of ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2009.518
更新日期：2010-04-01 00:00:00
abstract：:Polycystic renal disease was induced in rats by feeding 2-amino-4,5-diphenylthiazole. Tubular (TBM) and glomerular basement membranes (GBM) were purified and analyzed for possible structural changes that may be a factor in the development of the tubular dilations and cysts. Changes in the relative quantities of TBM po...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1985.193
更新日期：1985-11-01 00:00:00
abstract：:Calcitonin secretion is stimulated by acute hypercalcemia. Furthermore, in the rat, the calcemic response to parathyroid hormone (PTH) is decreased by calcitonin stimulation. However, in renal failure, it is not known if an increase in the serum calcium concentration within the physiologic range of serum calcium stimu...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1991.263
更新日期：1991-10-01 00:00:00
abstract：:Murine double minute (MDM)-2, an E3 ubiquitin ligase, promotes cancer cell survival and growth, by degrading the cell cycle regulator p53. Antagonism of MDM2 by the small-molecule cis-imidazoline nutlin analogs is under current study for cancer therapy. To test whether MDM2 also promotes regenerative cell growth, we d...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2011.482
更新日期：2012-06-01 00:00:00
abstract：:Because of high risk of cardiovascular disease, patients with chronic kidney disease may benefit from cholesterol-lowering therapy beyond statins. A cost-effectiveness analysis of adding ezetimibe to high-dose statins for primary cardiovascular disease prevention in patients with non-dialysis-dependent chronic kidney ...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1016/j.kint.2019.02.029
更新日期：2019-07-01 00:00:00
abstract：:The pathologic and clinical features of 16 patients with dense intramembranous deposit disease are described. By light microscopy nine patients had membranoproliferative glomerulonephritis, five had focal segmental necrotizing glomerulonephritis with segmental epithelial crescents, four of whom also had a prominent tu...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1984.71
更新日期：1984-04-01 00:00:00
abstract：:This study was undertaken to test the hypothesis that, given equal arterial pressure reductions, the combination of an angiotensin converting enzyme (ACE) inhibitor and calcium antagonist slows declines in renal function and yields greater reductions in albuminuria over either agent alone. This hypothesis was evaluate...
journal_title：Kidney international
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/ki.1992.139
更新日期：1992-04-01 00:00:00
abstract：:Chronic cyclosporine (CsA) nephrotoxicity is a major complication of heart, bone marrow, and renal transplantation, and is characterized in humans by striped interstitial fibrosis, tubular dilatation and atrophy, and hyalinization of hilar arterioles. This last feature is highly specific for cyclosporine injury and ha...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1995.311
更新日期：1995-08-01 00:00:00
abstract：:The current study was undertaken to examine the effects of dithiothreitol (DDT), a sulfhydryl-reducing agent and heavy metal chelator, on the course of heavy metal-induced acute renal failure in the rat. Groups of rats in metabolic cages received uranyl nitrate (UN) alone, UN plus DTT, mercuric chloride (HgCl2) alone,...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1977.88
更新日期：1977-08-01 00:00:00
abstract：:Hyper-activation of Rac1, a small GTPase, in glomerular podocytes has been implicated in the pathogenesis of familial proteinuric kidney diseases. However, the role of Rac1 in acquired nephrotic syndrome is unknown. To gain direct insights into this, we generated a transgenic mouse model expressing a doxycycline-induc...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2017.03.010
更新日期：2017-08-01 00:00:00
abstract：:Adenosine is known to decrease renal blood flow and glomerular filtration rate. We have tested the hypothesis that adenosine exerts contractile effects on mesangial cells. Furthermore, we have studied, using selective agonists and antagonists for adenosine, which kind of adenosine receptor, A1 or A2, is mainly implica...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1989.126
更新日期：1989-06-01 00:00:00
