Abstract:
:Mitochondria are critical in determining a cell's energy homeostasis and fate, and mitochondrial dysfunction has been implicated in the pathogenesis of chronic kidney disease (CKD). We sought to identify causative mitochondrial microRNAs. A microarray screen of kidney tissue from healthy mice identified 97 microRNAs that were enriched in the mitochondrial fraction. We focused on microRNA-214-3p (miR-214) because of a very high ratio of mitochondrial to cytoplasmic expression in the kidney compared to other organs. Tubular expression of miR-214 was more abundant in kidney tissue from patients with CKD than from healthy controls, and was positively correlated with the degree of proteinuria and kidney fibrosis. Expression of miR-214 was also increased in the kidney of mouse models of CKD induced by obstruction, ischemia/reperfusion, and albumin overload. Proximal tubule-specific deletion of miR-214 attenuated apoptosis, inflammation, fibrosis, and mitochondrial damage in these CKD models. Pharmacologic inhibition of miR-214 had a similar effect in the albumin overload model of CKD. In vitro, overexpressing miR-214 in proximal tubular cell lines induced apoptosis and disrupted mitochondrial oxidative phosphorylation, while miR-214 expression was upregulated in response to a variety of insults. The mitochondrial genes mt-Nd6 and mt-Nd4l were identified as the specific targets of miR-214 in the kidney. Together, these results demonstrate a pathogenic role of miR-214 in CKD through the disruption of mitochondrial oxidative phosphorylation, and suggest the potential for miR-214 to serve as a therapeutic target and diagnostic biomarker for CKD.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Bai M,Chen H,Ding D,Song R,Lin J,Zhang Y,Guo Y,Chen S,Ding G,Zhang Y,Jia Z,Huang S,He JC,Yang L,Zhang Adoi
10.1016/j.kint.2018.12.028subject
Has Abstractpub_date
2019-06-01 00:00:00pages
1389-1404issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(19)30114-0journal_volume
95pub_type
杂志文章abstract:BACKGROUND:Tacrolimus is a relatively new calcineurin inhibitor that has been increasingly used in transplant medicine. The objective of the current work is to report our preliminary experience with tacrolimus in the treatment of diffuse proliferative glomerulonephritis in systemic lupus erythematosus (SLE). METHODS:N...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1111/j.1523-1755.2005.00461.x
更新日期:2005-08-01 00:00:00
abstract::To evaluate the underlying mechanism of the putative renal protective effects of angiotensin converting enzyme (ACE) inhibitors, the modulatory action of captopril on the angiotensin II (Ang II) and platelet-derived growth factor (PDGF)-induced increase of cytosolic free calcium concentration ([Ca2+]i) was investigate...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.323
更新日期:1994-09-01 00:00:00
abstract:BACKGROUND:To study the molecular mechanism responsible for cadmium-induced Fanconi syndrome, an in vitro mouse model has been used. We have previously shown that exposure of primary cultures of kidney cortical cells to micromolar concentrations of cadmium inhibited uptake of the glucose analog, [14C] methyl alpha-d-gl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00201.x
更新日期:2003-10-01 00:00:00
abstract::The contractile properties of recombinant human erythropoietin (rHuEPO) on isolated resistance vessels of renal and mesenteric vascular beds were studied in an in vitro model using a small vessel myograph. Under isometric conditions, rHuEPO caused a contraction of this vasculature in a concentration range between 10 U...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.31
更新日期:1991-02-01 00:00:00
abstract::Previously, uremic toxins were sometimes regarded as a large, mysterious, but also anonymous group of factors potentially contributing to morbidity and mortality in end-stage renal disease. By identifying the protein-bound solute p-cresol as a risk factor for mortality in dialysis patients, Bammens and colleagues for ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5000236
更新日期:2006-03-01 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:BACKGROUND:Dialysis efficiency has a great influence on the outcome of patients. Few data are available on the removal of solutes with molecular weights higher than urea and creatinine. The aim of our study was to assess the transport and the removal of substances with molecular weights up to 15 kD and to evaluate the ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00216.x
更新日期:2002-03-01 00:00:00
abstract:BACKGROUND:The ontogeny of the renal mineralocorticoid (MR) and glucocorticoid (GR) receptors in the ovine fetus, and the effects of early exposure to synthetic or natural glucocorticoids on the expression of these genes in late gestation were examined. METHODS:A partial cDNA sequence for the ovine MR was cloned and u...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00157.x
更新日期:2002-02-01 00:00:00
abstract:BACKGROUND:Both high glucose (HG) and angiotensin II (Ang II) causes glomerular mesangial cell (GMC) growth and increased synthesis of matrix proteins like collagen IV contributing to diabetic nephropathy. We have recently found that exposure of vascular smooth muscle cells to HG augments the Ang II activation of the g...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00311.x
更新日期:2002-05-01 00:00:00
abstract::Absorption of amino acids by the necturus proximal tubules was measured under free-flow conditions The coexistence of proximal tubular amino acid influx was determined by infusing saline into tubular lumens by the stopped-flow microperfusion technique. Under free-flow conditions, fractional absorption of individual am...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1978.67
更新日期:1978-06-01 00:00:00
abstract::In Australia, Canada, New Zealand, and the United States indigenous people have high rates of chronic kidney disease but poor access to effective therapies. To more fully define these issues, we compared the demographics of renal transplantation of indigenous patients in these 4 countries. Data encompassing 312,507 in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.236
更新日期:2009-09-01 00:00:00
abstract::Bone marrow (BM) cells are reported to contribute to the process of regeneration following myocardial infarction. The present study examined two independent clonal studies to determine the origin of bone marrow (BM)-derived cardiomyocytes. First, we transplanted single CD34(-)c-kit(+)Sca-1(+)lineage(-) side population...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1111/j.1523-1755.2005.00624.x
更新日期:2005-11-01 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:BACKGROUND:A family history increases the risk of kidney stone passage independent of dietary risk factors. However, the metabolic basis for familial aggregation of urolithiasis is unknown. METHODS:We evaluated metabolic risk factors in families with at least two sibs with a history of calcium stones. Sibs underwent o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0600031141.x
更新日期:2001-09-01 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::In summary, the three major segments of the collecting duct subserve three different functions in the urinary concentrating mechanism. The main function of the cortical collecting tubule is to raise the fractional solute contribution and absolute concentration of urea in fluid that it delivers to the outer medullary c...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1987.41
更新日期:1987-02-01 00:00:00
abstract::McAdoo et al. propose that patients with both circulating antiglomerular basement membrane antibody and antineutrophil cytoplasm antibody demonstrate a phenotype that lies between that of single-positive antiglomerular basement membrane disease and antineutrophil cytoplasm antibody-associated vasculitis. Specifically,...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2017.04.024
更新日期:2017-09-01 00:00:00
abstract::The content of platelet activating factor (PAF) in glomeruli isolated from rats with nephrotoxic serum glomerulonephritis (NSGN) was quantified at various stages of the disease and the role of complement, platelets and neutrophils in mediating changes in glomerular PAF levels was evaluated. PAF content was assessed fo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.40
更新日期:1990-02-01 00:00:00
abstract:BACKGROUND:Macrophage-mesangial cell interaction plays a crucial role in the pathogenesis of glomerulonephritis. We established a novel system for continuous, real-time monitoring of cross-talk between macrophages and mesangial cells in vitro and ex vivo. METHODS:Rat mesangial cells were genetically engineered to prod...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00471.x
更新日期:2005-08-01 00:00:00
abstract::The monoclonal antibody (mAb) 3G5 was found, by indirect immunofluorescence, to bind to renal cortical structures in frozen sections of human, rat and calf kidneys. Double indirect immunofluorescence studies on frozen sections of rat kidneys showed that 3G5 stained only the glomerulus and the distribution of the 3G5 a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.236
更新日期:1992-06-01 00:00:00
abstract::Lysophosphatidic acid (LPA) is known to regulate various biological responses by binding to LPA receptors. The serum level of LPA is elevated in diabetes, but the involvement of LPA in the development of diabetes and its complications remains unknown. Therefore, we studied LPA signaling in diabetic nephropathy and the...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.11.010
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND:Hyperlipidemia is a risk factor for long-term renal transplant dysfunction, but no prospective clinical trials have investigated the effects of statin treatment on graft function in renal transplant recipients. The aim of the present study was to evaluate the effect of fluvastatin on long-term renal transpla...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2004.00919.x
更新日期:2004-10-01 00:00:00
abstract:BACKGROUND:Hypertriglyceridemia is a result of reduced triglyceride (TG)-rich lipoprotein (TRL) catabolism and occurs in rats with nephrotic syndrome (NS) and in Nagase analbuminemic rats (NARs). While the heparin-releasable lipoprotein lipase (LpL) pool in NAR and in NS is similar, TG levels are significantly greater ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00478.x
更新日期:2001-01-01 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:BACKGROUND:The link between dialysis "vintage" (length of time on dialysis in months to years) and survival has been difficult to define, largely because of selection effects. End-stage renal disease (ESRD) is thought to be a wasting illness, but there are no published reports describing the associations between vintag...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00945.x
更新日期:2000-03-01 00:00:00
abstract::Angiotensin II plays an important role in the regulation of blood pressure, body salt and fluid balance, and urine concentration. Mice with deletion of the AT(1a) receptor develop polyuria and urine concentration defects. We studied the mechanisms of these urine concentration defects by treating wild-type and AT(1a)-k...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.134
更新日期:2009-07-01 00:00:00
abstract::Simple life-table analyses have not identified the reasons for the steady improvement over the years in graft survival. The use of more sophisticated multifactorial statistical techniques is indicated to identify prognostic factors and to explore the "center effect" on graft survival. An agenda for retrospective analy...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.188
更新日期:1983-10-01 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::Many subjects nowadays present with end-stage renal failure and its attendant cardiovascular complications without known prior renal damage. In this report we review the evidence available to strongly suggest that the present practice of secondary prevention in those with known prior renal disease should be extended t...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1111/j.1523-1755.2004.66001.x
更新日期:2004-12-01 00:00:00
abstract::The existence of a tissue renin-angiotensin (RAS) system independent of the circulating RAS has prompted the search for cellular binding sites for angiotensinogen and for renin in order to explain their tissue uptake. Two receptors that bind with similar affinity mature renin and prorenin were identified, the mannose-...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5000265
更新日期:2006-05-01 00:00:00