Abstract:
:High glucose evokes a variety of signals in mesangial cells that alter cellular functions responsible for the development of diabetic glomerulopathy. The hypoxia-inducible factor-1alpha (HIF-1alpha) regulates cellular homeostasis under hypoxic conditions, but it also has pleiotropic effects in response to cellular stresses at normoxia. Here we determined whether HIF-1alpha has a role in the regulation of mesangial cells in hyperglycemia. In the streptozotocin-induced diabetic mouse model, glomerular mesangial cells had a significant increase in HIF-1alpha expression in the nucleus. In cultured mesangial cells, high glucose enhanced the expression of HIF-1alpha and its target genes known to be involved in the development of diabetic glomerulopathy. A glucose-responsive carbohydrate response element binding protein (ChREBP) was found to have a critical role in the transcriptional upregulation of HIF-1alpha and downstream gene expression in mesangial cells exposed to high glucose. Knockdown of HIF-1alpha or ChREBP in mesangial cells abrogated the high glucose-mediated perturbation of gene expression. Our results show that ChREBP and HIF-1alpha mediate gene regulation in mesangial cells. Further studies will be needed to find out whether these findings are relevant to the development of the diabetic nephropathy.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Isoe T,Makino Y,Mizumoto K,Sakagami H,Fujita Y,Honjo J,Takiyama Y,Itoh H,Haneda Mdoi
10.1038/ki.2010.99subject
Has Abstractpub_date
2010-07-01 00:00:00pages
48-59issue
1eissn
0085-2538issn
1523-1755pii
S0085-2538(15)54406-2journal_volume
78pub_type
杂志文章abstract::To maintain nitrogen equilibrium when prescribed a low protein diet (LPD), metabolic adaptations occur involving a reduction protein turnover, principally decreased muscle protein degradation. Studies suggest that in patients with chronic renal failure (CRF) uncomplicated by metabolic acidosis (MA), these adaptive res...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.275
更新日期:1991-10-01 00:00:00
abstract:BACKGROUND:The tissue renin-angiotensin system (RAS) may modulate the structural and functional changes that occur in the diabetic kidney. METHODS:Hypertensive transgenic (mREN-2)27 rat (TGR) that exhibit increased tissue renin expression were administered streptozotocin (STZ, diabetic) or citrate buffer (non-diabetic...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00019.x
更新日期:1998-08-01 00:00:00
abstract::Low-protein diets (LPD) increase insulin-mediated glucose disposal in chronic renal failure (CRF), but the fate of the better utilized glucose and the effect on energy production rate are unknown. Using a two-step (1 and 5 mU x kg(-1) x min(-1)) euglycemic hyperinsulinemic clamp combined with indirect calorimetry, we ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.167
更新日期:1997-04-01 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::To determine whether Cyclosporine A (CsA) alters the intrarenal expression of the renin and type 1 angiotensin II receptor genes, male adult Sprague-Dawley rats were given 25 mg/kg/day CsA s.c. for three weeks (CsA, N = 20) and were compared to pair-fed vehicle treated rats (Con, N = 20). The intrarenal distribution o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.90
更新日期:1993-03-01 00:00:00
abstract::Plasma lipid and lipoprotein concentration and high density lipoprotein (HDL) kinetics were determined in control subjects and patients with chronic renal failure (CRF). Results demonstrated that plasma triglyceride (TG) concentration was significantly higher (P less than 0.001) in patients with CRF, associated with a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.114
更新日期:1990-05-01 00:00:00
abstract::The ankyrin repeat and sterile α motif (SAM) domain-containing six gene (Anks6) is a candidate for polycystic kidney disease (PKD). Originally identified in the PKD/Mhm(cy/+) rat model of PKD, the disease is caused by a mutation (R823W) in the SAM domain of the encoded protein. Recent studies support the etiological r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.122
更新日期:2015-08-01 00:00:00
abstract::Despite the increasing knowledge of the role of gangliosides in normal and diseased tissues, little is known of the presence, distribution and functions of these molecules in the kidney. In this study we analyzed the main gangliosides of isolated glomeruli and cortical, medullary and papillary fractions of the human, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.14
更新日期:1994-01-01 00:00:00
abstract::In studying the metabolic effects of diet potassium (K+) variation in normal humans, we noted that varying diet K+ within its normal range influenced inorganic phosphorus (Pi) homeostasis and serum calcitriol (1,25-dihydroxyvitamin D) levels. In six men who ingested a constant whole-foods diet containing (per 70 kg bo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.120
更新日期:1990-05-01 00:00:00
abstract::Platelet activating factor (PAF) is a potent lipid mediator with a broad range of biologic activities. Experimental evidence suggests that PAF plays a role in the pathogenesis of a variety of inflammatory processes including allograft rejection. In this study, we evaluated the effects of the PAF antagonist BN52021 on ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.301
更新日期:1995-08-01 00:00:00
abstract:BACKGROUND:The relationship between low hematocrit and contrast-induced nephropathy has not been investigated. METHODS:Of 6,773 consecutive patients treated with percutaneous coronary intervention, contrast-induced nephropathy (an increase of >/=25% or >/=0.5 mg/dL in preprocedure serum creatinine, at 48 hours postpro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.67131.x
更新日期:2005-02-01 00:00:00
abstract::Cell-cycle proteins influence almost all aspects of embryogenesis and differentiation. In adults, these proteins control cell division and regeneration after injury. During the past several years, their roles in controlling reaction to stress have been demonstrated in several organ systems. In the kidney, the cell typ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2009.562
更新日期:2010-04-01 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::When the endotoxin-lipopolysaccharide (LPS) derived from the cell wall of gram-negative bacteria is given to the rat in vivo, there are prompt, marked decreases in glomerular filtration rate (GFR), renal blood flow (RBF) and % Na+ reabsorption (%T-Na+). However, it has not been determined whether the endotoxin itself ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.105
更新日期:1990-05-01 00:00:00
abstract:BACKGROUND:Endothelium-derived nitric oxide and reactive oxygen species (ROS) have been proposed to regulate vascular tone by complex mechanisms, including the modulation of ion channel function. In endothelial function itself, activation of Ca2+-activated K+ channels (KCa) plays a crucial role by inducing hyperpolariz...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00051.x
更新日期:2003-07-01 00:00:00
abstract::LECT2 amyloidosis is the latest systemic type of amyloidosis to be described. It was discovered in patients with nephrotic syndrome and renal failure and is characterized by amyloid deposition in glomeruli, renal vessels, and interstitium. Clinical and pathological features of earlier phases of this type of amyloidosi...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2010.18
更新日期:2010-05-01 00:00:00
abstract::Tenofovir, a widely prescribed antiretroviral medication for treatment of HIV-1 infection, is infrequently associated with renal dysfunction and biopsy findings of acute tubular necrosis. We examined the clinical and pathological findings in 13 cases of tenofovir nephrotoxicity (7 men and 6 women, mean age of 51.1±9.6...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.318
更新日期:2010-12-01 00:00:00
abstract::Urinary exosomes have received considerable attention as a potential biomarker source for the diagnosis of renal diseases. Notwithstanding, their use in protein biomarker research is hampered by the lack of efficient methods for vesicle isolation, lysis, and protein quantification. Here we report an improved ultracent...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.25
更新日期:2012-06-01 00:00:00
abstract::Before hemodialysis, patients have an intraerythrocytic pH (pHi) and an extracellular pH, measured in whole blood (pHo), which are lower than those of healthy controls. During bicarbonate hemodialysis, pHi values continuously increase, approaching a normal value at the end of the session. Concomitantly, pHo values fol...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.66
更新日期:1989-03-01 00:00:00
abstract:BACKGROUND:Angiotensin II (Ang II) can up-regulate nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase, whose product superoxide anion (O2-) can interact with nitric oxide (NO) to form peroxynitrite (ONOO-). We tested the hypothesis that Ang II subtype 1 (AT1) receptor activation enhances oxidative stress and...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00123.x
更新日期:2002-01-01 00:00:00
abstract::Chronic inflammation is a complication of conventional hemodialysis that induces progressive cardiovascular damage. An apparently straightforward manipulation to treat this-removal of a large amount of uremic toxins by convection-has proven that the relationships between inflammation and convective techniques such as ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.81
更新日期:2014-08-01 00:00:00
abstract:BACKGROUND:Low dietary phosphorus (P) prevents parathyroid gland (PTG) hyperplasia and the development of secondary hyperparathyroidism (SH) in uremic rats. The present study explores the effects of P restriction on parathyroid hormone (PTH) synthesis and secretion and PT cell growth in rats with established SH and PTG...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00265.x
更新日期:2002-04-01 00:00:00
abstract::The renal 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) enzyme inactivates 11-hydroxy steroids in the kidney, thus protecting the nonselective mineralocorticoid receptor (MR) from occupation by glucocorticoids. The gene is highly expressed in all sodium-transporting epithelia, but also in human placenta, pan...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1046/j.1523-1755.2000.00978.x
更新日期:2000-04-01 00:00:00
abstract:BACKGROUND:The aims of the present study were to determine the prevalence of inducible myocardial ischemia (IMI) in renal transplant recipients (RTR) more than 50 years old, to identify predictors of IMI, and to search for its prognostic value. METHODS:Among the 377 renal transplantations performed between 1989 and 19...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00929.x
更新日期:2004-10-01 00:00:00
abstract::The improvement in the anemia in patients with end-stage renal disease (ESRD) on continuous ambulatory peritoneal dialysis (CAPD) suggests that dialyzable substances present in the sera of uremic patients either inhibit erythropoiesis directly or inactivate erythropoietin (EPO). In the present study predialysis sera f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.88
更新日期:1991-04-01 00:00:00
abstract::We studied the effect of three antihypertensive drugs on the growth of glomeruli in four- to five-week-old Munich-Wistar rats (N = 24), which were undergoing rapid maturation processes. Young rats were given an angiotensin converting enzyme inhibitor (ACEI, enalapril, 50 mg/liter drinking water), verapamil (50 mg/lite...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.314
更新日期:1990-12-01 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
abstract:BACKGROUND:Bicarbonate reabsorption in the kidney proximal tubule is predominantly mediated via the apical Na+/H+ exchanger (NHE-3) and basolateral Na+: HCO(-3) cotransporter (NBC-1). The purpose of these studies was to examine the effects of Na+ load and altered acid-base status on the expression of NHE-3 and NBC-1 in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00995.x
更新日期:2001-11-01 00:00:00
abstract::Transepithelial fluid secretion promotes the progressive enlargement of cysts in autosomal dominant polycystic kidney disease (ADPKD). Recent indirect evidence indicated that active chloride transport may drive net fluid secretion in cultures of epithelia derived from ADPKD cysts. We now report that forskolin, which s...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.304
更新日期:1996-07-01 00:00:00
abstract::Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a potent microvascular permeability-enhancing mediator as well as a selective mitogen for vascular endothelium. In this study, in situ hybridization and immunohistochemistry co-localized VPF mRNA and protein to glomerular v...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.441
更新日期:1992-12-01 00:00:00