Abstract:
:Ischemia-reperfusion occurs in a great many clinical settings and contributes to organ failure or dysfunction. CD154-CD40 signaling in leukocyte-endothelial cell interactions or T-cell activation facilitates tissue inflammation and injury. Here we tested a siRNA anti-CD40 in rodent warm and cold ischemia models to check the therapeutic efficacy and anti-inflammatory outcome of in vivo gene silencing. In the warm ischemia model different doses were used, resulting in clear renal function improvement and a structural renoprotective effect. Renal ischemia activated the CD40 gene and protein expression, which was inhibited by intravenous siRNA administration. CD40 gene silencing improved renal inflammatory status, as seen by the reduction of CD68 and CD3 T-cell infiltrates, attenuated pro-inflammatory, and enhanced anti-inflammatory mediators. Furthermore, siRNA administration decreased a spleen pro-inflammatory monocyte subset and reduced TNFα secretion by splenic T cells. In the cold ischemia model with syngeneic and allogeneic renal transplantation, the most effective dose induced similar functional and structural renoprotective effects. Our data show the efficacy of our siRNA in modulating both the local and the systemic inflammatory milieu after an ischemic insult. Thus, CD40 silencing could emerge as a novel therapeutic strategy in solid organ transplantation.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
de Ramon L,Ripoll E,Merino A,Lúcia M,Aran JM,Pérez-Rentero S,Lloberas N,Cruzado JM,Grinyó JM,Torras Jdoi
10.1038/ki.2015.146subject
Has Abstractpub_date
2015-09-01 00:00:00pages
538-49issue
3eissn
0085-2538issn
1523-1755pii
S2157-1716(15)32210-3journal_volume
88pub_type
杂志文章abstract::Insulin resistance from chronic kidney disease (CKD) stimulates muscle protein wasting but mechanisms causing this resistance are controversial. To help resolve this, we used microarray analyses to identify initiators of insulin resistance in the muscles of mice with CKD, glucose intolerance, and insulin resistance. C...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.97
更新日期:2013-08-01 00:00:00
abstract:BACKGROUND:The cyclopentenone prostaglandin 15-deoxy-delta12,14-prostaglandin J2 (15dPGJ2) affects mesangial proliferation, survival and production of proinflammatory proteins. During a survey of the mesangial cell proteome after treatment with 15dPGJ2, heat shock protein 70 (HSP70) was found to be the most conspicuous...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00454.x
更新日期:2004-03-01 00:00:00
abstract:BACKGROUND:The purpose of this study was to examine the lipid abnormalities associated with urinary albumin excretion rate (UAER) in type 2 diabetic patients. METHODS:A total of 275 (122 men and 153 women; aged 60.6 +/- 11.1 years) patients were selected with stringent criteria to prevent confounders. Normoalbuminuria...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00235.x
更新日期:2005-04-01 00:00:00
abstract::During the heterologous phase of experimental anti-glomerular basement membrane (anti-GBM) nephritis, leukocyte influx peaks within hours, whereas albuminuria occurs within 1 day. In the subsequent autologous phase, endogenous anti-GBM IgG develops and albuminuria persists. Heparan sulfate (HS) proteoglycans like synd...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002514
更新日期:2007-11-01 00:00:00
abstract::Alterations in myocardial wall texture stand out among ADPKD cardiovascular manifestations in hypertensive and normotensive patients. To elucidate their pathogenesis, we analyzed the cardiac phenotype in Pkd1(cond/cond)Nestin(cre) (CYG+) cystic mice exposed to increased blood pressure, at 5 to 6 and 20 to 24 weeks of ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.04.028
更新日期:2016-09-01 00:00:00
abstract::Renal function measurement by clearance methods relies on accurately timed urine collection. In small experimental animals, renal function measurement is usually performed under anesthesia and/or with the application of bladder catheters to ensure accurate urine collection. To avoid both anesthesia and the need for bl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.327
更新日期:1997-07-01 00:00:00
abstract::Cytomegalovirus (CMV) seropositivity is associated with increased risk for atherosclerotic disease in patients with end-stage renal disease. This association is due to a unique peripheral blood CD4(+) T cell population which lack CD28 (CD4(+)CD28(-) T cells). Here we found that this patient population has a significan...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.301
更新日期:2008-09-01 00:00:00
abstract::Disturbed pulsatile LH secretion has been suggested to play a role in the etiology of delayed puberty and disturbed reproductive function in chronic renal failure (CRF), but interpretation of gonadotropin secretion from plasma concentration measurements is confounded by alterations in hormone metabolic clearance. To s...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1038/ki.1994.191
更新日期:1994-05-01 00:00:00
abstract:BACKGROUND:Adrenomedullin (ADM) exerts antiproliferative effects on rat mesangial cells in vitro and, therefore is a possible renoprotective agent. In contrast, nitric oxide (NO) is capable of exerting both cytoprotective and cytotoxic actions. It was the objective of the present study to examine whether NO stimulates ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00330.x
更新日期:2002-05-01 00:00:00
abstract::We examined the role of the plasminogen activator/plasmin system in extracellular matrix (ECM) degradation by human mesangial cells cultured on thin films of 125I-labeled ECM (Matrigel). ECM degradation (release of 125I into the medium) was dependent on exogenous plasminogen, proportional to the number of mesangial ce...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.150
更新日期:1995-04-01 00:00:00
abstract::It has been shown that somatostatin inhibits the antidiuretic action of vasopressin in toad urinary bladder in vitro and in dogs and rats in vivo. The presence of somatostatin-like immunoreactivity (SLI) in the urinary bladder and kidney of the toad has suggested the possibility that somatostatin may act as a local pa...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.223
更新日期:1983-12-01 00:00:00
abstract::Coronary artery stenosis induces renal inflammation and kidney injury in pigs even in the absence of myocardial infarction or clinically significant heart failure. This effect is aggravated by experimentally induced renovascular hypertension. Interestingly, oxidative stress originating from the ischemic myocardium was...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.431
更新日期:2015-04-01 00:00:00
abstract::To investigate the cause and the mechanisms responsible of the compulsive thirst and excessive fluid intake observed in many patients on chronic dialysis treatment, we measured plasma antidiuretic hormone (ADH), angiotensin II (Ang II) and some hemodynamic parameters in seven polydipsic and in six normodipsic patients...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.219
更新日期:1993-07-01 00:00:00
abstract::Class IV-S lupus nephritis is often associated with more necrosis and fewer subendothelial immune deposits compared to class IV-G lupus nephritis, suggestive of necrotising glomerular inflammation found in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. ANCAs are present in a significant proportion o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.04.029
更新日期:2017-11-01 00:00:00
abstract::This study evaluated risk factors for end-stage renal disease (ESRD) and the prognostic significance of serum creatinine levels in a community-based mass screening. We used the registries of both community-based mass screening and chronic dialysis programs. In 1983, a total of 107,192 subjects over 18 years of age (51...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.119
更新日期:1997-03-01 00:00:00
abstract:BACKGROUND:Although atherosclerotic renovascular disease is increasingly recognized in chronic kidney disease, few national level studies have examined its clinical epidemiology. METHODS:Claims data from a 5% random sample of the United States Medicare population were used to select patients without atherosclerotic re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00406.x
更新日期:2005-07-01 00:00:00
abstract:BACKGROUND:Optimal nutrient intake is important in the maintenance of a positive nitrogen balance in hemodialysis (HD) patients. The objectives of this study were (1) to assess the influence of two levels of protein intakes on nitrogen balance in stable adult HD patients, and (2) to identify a minimum level of protein ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00171.x
更新日期:2000-07-01 00:00:00
abstract:BACKGROUND:Chemokine receptor 5 (CCR5) plays an important role in the recruitment of monocytes and T cells in inflammation and experimental studies suggest that CCR5 might be involved in the pathogenesis of IgA nephropathy. A mutation in the CCR5 gene (CCR5 Delta32), leading to a nonfunctional receptor, was recently de...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00057.x
更新日期:2005-01-01 00:00:00
abstract::Tubulointerstitial nephritis antigen (TIN-ag) is an extracellular matrix (ECM) glycoprotein that has been recently isolated and cloned from the rabbit kidney. It is an integral component of the basal lamina, and unlike other basement membrane proteins it is exclusively expressed in the tubular basement membranes (TBMs...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.375
更新日期:1997-09-01 00:00:00
abstract::A major problem in cyclosporine A (CsA) therapy is its nephrotoxicity, characterized by a marked fall in glomerular filtration rate (GFR). Since the glomerular ultrafiltration area is an important determinant of GFR and has been proposed to be regulated by mesangial (MS) cell contraction, we examined the effect of CsA...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.149
更新日期:1988-07-01 00:00:00
abstract:BACKGROUND:Adiponectin is an adipocyte-derived cytokine that has anti-inflammatory properties. A preliminary proteomic evaluation of urine for biomarkers of systemic lupus erythematosus (SLE) nephritis demonstrated high levels of adiponectin in SLE urine. This prompted investigation of adiponectin expression in human S...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00601.x
更新日期:2005-10-01 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::Clinical and experimental studies have shown that serum aluminum (Al) is bound to transferrin and that cellular uptake of Al appears to be mediated by transferrin receptors. Based on these findings it is widely believed that intestinal Al absorption occurs via iron-specific, transferrin-dependent pathways and that iro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.509
更新日期:1996-12-01 00:00:00
abstract::To define the pattern of recovery from postischemic acute renal failure (ARF), we performed clearance and micropuncture studies at intervals of 1, 2, 4, and 8 weeks following 60 min of complete unilateral renal artery occlusion in the rat. At 1 week, the inulin clearance (CIn) of the postischemic kidney was less than ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1979.112
更新日期:1979-08-01 00:00:00
abstract::Genetic deletion of the adenosine A1 receptor (A1AR) increased renal injury following ischemia-reperfusion injury suggesting that receptor activation is protective in vivo. Here we tested this hypothesis by expressing the human-A(1)AR in A(1)AR knockout mice. Renal ischemia-reperfusion was induced in knockout mice 2 d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.699
更新日期:2009-04-01 00:00:00
abstract::Although APOL1 high-risk genotype partially accounts for the increased susceptibility of blacks to chronic kidney disease (CKD), whether APOL1 associates differentially with mortality risk remains controversial. Here we evaluate the association between APOL1 genotype and risk of death and determine whether APOL1 statu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.09.033
更新日期:2017-02-01 00:00:00
abstract::Toward an etiological classification of developmental disorders of the kidney and upper urinary tract. There are a large number of developmental disorders and syndromes that affect the kidney and upper urinary tract. These have generally been classified according to morphological criteria established decades ago. Alth...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1046/j.1523-1755.2002.00086.x
更新日期:2002-01-01 00:00:00
abstract::Fourteen Center hemodialysis (CHD) patients, 13 continuous ambulatory peritoneal dialysis (CAPD) patients, and 10 normals matched by group for age and sex were compared using a battery of evoked (EP) and event-related (ERP) brain potential measures to determine the effects on central nervous system (CNS) functioning o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.279
更新日期:1986-12-01 00:00:00
abstract::The International Pediatric Peritonitis Registry (IPPR) was created to assess and evaluate the validity of the pediatric peritonitis treatment guidelines issued by the International Society for Peritoneal Dialysis. The study by Schaefer et al., one of the first to emerge from the IPPR, describes regional variability i...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002529
更新日期:2007-12-01 00:00:00
abstract::Cell surface aminopeptidases N (APN) and A (APA) have been characterized on cultured human glomerular epithelial cells and a SV40-transformed cell line derived from them. APN had a wide substrate specificity whereas APA only attacked peptides with an acidic N terminal amino acid. Both enzymes also differed by their se...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.227
更新日期:1992-06-01 00:00:00