Abstract:
:Podocyte injury and loss contribute to the progression of glomerular diseases, including diabetic kidney disease. We previously found that the glomerular expression of Sirtuin-1 (SIRT1) is reduced in human diabetic glomeruli and that the podocyte-specific loss of SIRT1 aggravated albuminuria and worsened kidney disease progression in diabetic mice. SIRT1 encodes an NAD-dependent deacetylase that modifies the activity of key transcriptional regulators affected in diabetic kidneys, including NF-κB, STAT3, p53, FOXO4, and PGC1-α. However, whether the increased glomerular SIRT1 activity is sufficient to ameliorate the pathogenesis of diabetic kidney disease has not been explored. We addressed this by inducible podocyte-specific SIRT1 overexpression in diabetic OVE26 mice. The induction of SIRT1 overexpression in podocytes for six weeks in OVE26 mice with established albuminuria attenuated the progression of diabetic glomerulopathy. To further validate the therapeutic potential of increased SIRT1 activity against diabetic kidney disease, we developed a new, potent and selective SIRT1 agonist, BF175. In cultured podocytes BF175 increased SIRT1-mediated activation of PGC1-α and protected against high glucose-mediated mitochondrial injury. In vivo, administration of BF175 for six weeks in OVE26 mice resulted in a marked reduction in albuminuria and in glomerular injury in a manner similar to podocyte-specific SIRT1 overexpression. Both podocyte-specific SIRT1 overexpression and BT175 treatment attenuated diabetes-induced podocyte loss and reduced oxidative stress in glomeruli of OVE26 mice. Thus, increased SIRT1 activity protects against diabetes-induced podocyte injury and effectively mitigates the progression of diabetic kidney disease.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Hong Q,Zhang L,Das B,Li Z,Liu B,Cai G,Chen X,Chuang PY,He JC,Lee Kdoi
10.1016/j.kint.2017.12.008subject
Has Abstractpub_date
2018-06-01 00:00:00pages
1330-1343issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(18)30033-4journal_volume
93pub_type
杂志文章abstract::The beneficial effects of post-insult administration of pentoxifylline, a novel hemorheologic agent experimentally studied in various ischemic diseases, were evaluated in two models of acute renal failure (ARF): direct nephrotoxicity (mercuric chloride 4 mg/kg via femoral vein) and hemoglobinuria (glycerol 10 ml/kg i....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.218
更新日期:1989-09-01 00:00:00
abstract:BACKGROUND:Lipoprotein glomerulopathy (LPG) is characterized by intraglomerular lipoprotein thrombosis and high plasma concentrations of apolipoprotein (apo) E. An apo E variant, apo E2 (Arg145Pro) Sendai, was recently identified in three patients with LPG. We detected a novel point mutation in the apo E gene in a pati...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00572.x
更新日期:1999-08-01 00:00:00
abstract::Intrarenal artery infusions of hypertonic saline can activate tubuloglomerular feedback (TGF), decreasing renal blood flow (RBF) and glomerular filtration rate (GFR). The response to infusion of hypertonic saline is enhanced by salt depletion and attenuated by salt loading, but has not previously been investigated in ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.236
更新日期:1987-10-01 00:00:00
abstract::The biological action of calcitriol is mediated through a hormone-receptor complex interacting with nuclear chromatin. Interaction of the calcitriol receptor (VDR) with VDR response elements produces bioactive proteins which carry out the physiological actions of calcitriol. Since biological response to calcitriol app...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.252
更新日期:1994-07-01 00:00:00
abstract::Healthy male rats were exposed to a chronic ingesta of an isotonic NaCl solution during a period of four months. Two different preparations were utilized to study the effect of this treatment on the active mechanisms of Na+ reabsorption of kidney proximal tubular cells: outermost kidney cortex slices (rich in proximal...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.216
更新日期:1986-10-01 00:00:00
abstract::The inactivation of physiological glucocorticoids by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) confers mineralocorticoid specificity to certain aldosterone target tissues. Both NADP, and NAD-dependent isoforms of 11 beta-HSD have been described. An NAD-dependent isoform of 11 beta-HSD (11 beta-HSD2) was recen...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.39
更新日期:1996-01-01 00:00:00
abstract::Antibody-mediated rejection represents the first cause of graft loss in renal transplant recipients, and it is imperative to identify appropriate tools to enable risk stratification of such patients. Lately, the usefulness of measuring complement-binding anti-human leukocyte antigen (HLA) donor-specific antibodies (DS...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2018.06.032
更新日期:2018-10-01 00:00:00
abstract::The loss of interstitial capillaries is a feature of several experimental models of renal disease and this contributes to secondary kidney injury. Angiopoietin-1 is a secreted growth factor which binds to Tie-2 present on endothelia to enhance cell survival thereby stabilizing capillary architecture in-vitro. Previous...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.179
更新日期:2008-08-01 00:00:00
abstract::A major contributor to the development and progression of ischemia-reperfusion (IR)-induced acute renal failure (ARF) is the loss of functioning tubular epithelial cells by means of various cell deletion or death processes. Although the term "acute tubular necrosis" is still used to describe the pathology of ARF, this...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00701.x
更新日期:1999-10-01 00:00:00
abstract:BACKGROUND:It is not known to what extent intravascular phenotypic alterations in adhesion molecule expression induced by hemodialysis influence the recruitment of monocytes and their ability to up-regulate CD11b at the local site of inflammation in the interstitium. Using a skin suction chamber technique, we addressed...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00060.x
更新日期:2000-05-01 00:00:00
abstract::In chronic serum sickness, glomerular immune complexes form, yet C57BL/6 mice do not develop glomerulonephritis unless complement factor H (CfH) is absent, indicating the relevance of complement regulation. Complement receptor 3 (CD11b) and Fcγ receptors on leukocytes, and CfH on platelets, can bind immune complexes. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.373
更新日期:2015-05-01 00:00:00
abstract::Experimental studies have demonstrated the cardinal role played by the mononuclear phagocyte system in the removal of antigen-antibody complexes. To assess the functional capacity of phagocytes in patients with renal disease, 33 normal subjects, 10 patients with mesangial proliferative glomerulonephritis, 8 patients w...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.105
更新日期:1983-06-01 00:00:00
abstract:BACKGROUND:Although apoptosis has been linked to the renal cell deletion and ensuing renal fibrosis, its regulating mechanisms remain obscure. Of the known regulators of apoptosis, the best characterized is the Bax to Bcl-2 ratio. However, its importance in controlling apoptosis in glomerulonephritis is unclear. Here, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2002.kid587.x
更新日期:2002-10-01 00:00:00
abstract::Studies were undertaken to examine the mechanism whereby changes in intraluminal flow rates after reabsorption in the isolated perfused proximal tubule of the rabbit. All protocols employed the technique of in vitro perfusion of isolated segments of the proximal convoluted tubule. Stepwise elimination of d-glucose and...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.3
更新日期:1977-01-01 00:00:00
abstract:BACKGROUND:The obstructed kidney in unilateral ureteral obstruction (UUO) is characterized by renal atrophy and tissue loss, which is mediated by renal tubular apoptosis. We sought to determine whether NO is involved in renal tubular apoptosis in vitro and in vivo. METHODS:Rat renal tubular epithelial cells (NRK-52E) ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590041290.x
更新日期:2001-04-01 00:00:00
abstract::Renin secretion was compared in vivo and in vitro among five groups of rats, each group subjected to a different sodium balance for 10 to 14 days. The state of the renin-angiotensin system in vivo was evaluated by measuring the renal renin (RR) and the plasma renin concentration (PRC) in both anesthetized and nonanest...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.71
更新日期:1980-05-01 00:00:00
abstract::Organomercurial diuretics stimulate renin secretion although the underlying cellular mechanisms remain undefined. Since organomercurials are also known to react with sulfhydryl groups, the present studies determined the effects of sulfhydryl reagents on renin secretion. The effects of the non-diuretic mercurial agent,...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.57
更新日期:1989-03-01 00:00:00
abstract::Thrombotic microangiopathy (TMA) is a poorly recognized cause of collapsing glomerulopathy. The frequency and significance of collapsing glomerulopathy associated with renal TMA have not been specifically studied in native kidney biopsy specimens. Here we retrospectively documented clinicopathologic features of 53 pat...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.07.021
更新日期:2016-12-01 00:00:00
abstract::A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.10.014
更新日期:2020-11-07 00:00:00
abstract::Diabetes mellitus is associated with natriuresis, whereas estrogen has been shown to be renoprotective in diabetic nephropathy and may independently regulate renal sodium reabsorption. The aim of this study was to determine the effects of 17-beta estradiol (E(2)) replacement to diabetic, ovariectomized (OVX) female ra...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000140
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND:Candidate biomarkers for vasculopathy in systemic lupus erythematosus (SLE) include circulating endothelial cells and the recently identified endothelial protein C receptor (EPCR) which, when shed, promotes a thrombotic diathesis. This study sought correlation between plasma levels of soluble EPCR and diseas...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00385.x
更新日期:2005-07-01 00:00:00
abstract:BACKGROUND:The use of renal Kt/V (r-Kt/V) as an indicator for the need of dialysis initiation has been recommended in the NKF-DOQI guidelines. In analogy to clinical practice in peritoneal dialysis, a fall of r-Kt/V below a threshold of 2.0 per week may indicate inadequate renal toxin elimination. However, there are no...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00957.x
更新日期:2001-10-01 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::Progressive kidney fibrosis precedes end-stage renal failure in up to a third of patients with diabetes mellitus. Elevated intra-renal transforming growth factor-beta (TGF-beta) is thought to underlie disease progression by promoting deposition of extracellular matrix and epithelial-mesenchymal transition. GW788388 is...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002717
更新日期:2008-03-01 00:00:00
abstract:BACKGROUND:Inbred miniature swine treated for 12 days with high-dose cyclosporine A develop tolerance to histocompatibility complex (MHC) class I-mismatched renal allografts. When this protocol was modified by adding thymectomy before transplant, all animals developed acute rejection. Thereafter, by day 100, one half d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00440.x
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND:Hemodialysis access thrombosis is a significant cause of morbidity for hemodialysis patients and results from decreased access flow caused by venous outflow tract stenosis. Ultrasound dilution (UD) is a practical, noninvasive, and reliable indicator of access flow and is effective in predicting venous stenos...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.2001.00753.x
更新日期:2001-06-01 00:00:00
abstract::Erythropoietin (EPO) therapy in hemodialysis patients may be associated with an enhanced risk of vascular access and extracorporeal thrombosis. Assessment of blood coagulation and fibrinolysis was performed monthly on a group of 21 hemodialysis patients treated with EPO, and on four iron-deficient hemodialysis patient...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1993.229
更新日期:1993-07-01 00:00:00
abstract:BACKGROUND:Regular access monitoring is recommended to detect and treat access stenosis in order to prevent access thrombosis and failure. METHODS:In 1999, we instituted monthly access blood flow monitoring using the ultrasound dilution technique (UDT). In a sequential observational trial, 222 patients were studied fo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00697.x
更新日期:2005-11-01 00:00:00
abstract::The OSCAR study was a multicenter, prospective randomized open-label blinded end-point study of 1164 Japanese elderly hypertensive patients comparing the efficacy of angiotensin II receptor blocker (ARB) uptitration to an ARB plus calcium channel blocker (CCB) combination. In this prospective study, we performed presp...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/ki.2012.326
更新日期:2013-01-01 00:00:00
abstract::Twelve patients with progressive renal failure were placed on a very low protein diet supplemented by an essential amino acid-keto acid mixture for six to twelve months. Total daily intake was 0.04 g nitrogen/kg and 50 kcal/kg. Eight subjects had a significant change in the slope of reciprocal plasma creatinine, becom...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.99
更新日期:1986-05-01 00:00:00