Abstract:
BACKGROUND:Transforming growth factor-beta (TGF-beta) is known to play an important role in the pathophysiology of renal tubular disease. Researchers have recently identified a novel mitogen-activated protein kinase kinase kinase (MAPKKK), TAK (TGF-beta activated kinase)1, which stimulates the MKK3/6-p38K pathway. The purpose of our study was to investigate the functional role of the TAK1-MKK3/6-p38K pathway and classical MAPK cascades in the progression of the cell cycle in renal tubular cells. METHODS:The constitutive active form and negative form of TAK1 (TAK1dN and TAK1K63W, respectively), and active and negative forms of the p42/44 MAPK-activator, MKK1 (S222E and S222A, respectively) were transfected to LLC-PK1 cells. Western blot analyses and promoter-luciferase assay of cyclins D1, D2, D3, E, and A were performed, and cell cycle progression was analyzed by FACS scan. RESULTS:TAK1dN stimulated MKK6 and p38K activity and inhibited the percentage of the S and G2/M phases. TAK1K63 W inhibited TGF-beta-stimulated MKK6 and p38K activity. Cyclin D1 and cyclin A protein levels and promoter activities were negatively regulated by TAK1dN. In contrast, overexpression of the active form of p42/44 MAPK-activator, MKK1, increased cyclin D1 and A promoter activity and protein levels. CONCLUSION:The growth-inhibitory effects of TGF-beta are at least partially mediated by the TAK1-MKK6-p38K pathway. Cyclin D1 and A promoter activity and cell cycle progression in renal tubular cells are negatively regulated by the TAK1-MKK6-p38K pathway and positively regulated by the MKK1-p42/44MAPK pathway.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Terada Y,Nakashima O,Inoshita S,Kuwahara M,Sasaki S,Marumo Fdoi
10.1046/j.1523-1755.1999.00665.xsubject
Has Abstractpub_date
1999-10-01 00:00:00pages
1378-90issue
4eissn
0085-2538issn
1523-1755pii
S0085-2538(15)46447-6journal_volume
56pub_type
杂志文章abstract:BACKGROUND:While tubular cell death is a characteristic of acute renal failure (ARF), the molecular mechanisms that modulate this cell death are unclear. Cell fate in acute renal failure hinges on a balance of survival and mortality factors in a changing environment. We further explored this issue by studying selected ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00925.x
更新日期:2000-03-01 00:00:00
abstract::Hypocalcemia, hyperphosphatemia, and resistance to the action of PTH are well characterized features in the setting of advanced chronic renal failure (CRF). Although the underlying mechanisms are ill-understood, clinical and experimental evidence points to both PTH receptor down-regulation and post-receptor abnormalit...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.79
更新日期:1994-02-01 00:00:00
abstract::The natural course of idiopathic membranous nephropathy is variable, with some patients slowly progressing to renal failure while others maintain normal renal function over the entire time. Whether to treat this disease or not is controversial due to the lack of controlled data about the long-term effects of treatment...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1995.453
更新日期:1995-11-01 00:00:00
abstract::Isotomic fluid reabsorption (JV) of rat renal proximal tubules was examined by the shrinking droplet method in combination with simulatneous perfusion of blood capillaries. Sensitivity of JV measurement was improved by using each punctured tubule for control measurements: 1) Parathyroid hormoen (PTH) on the contralumi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.12
更新日期:1977-02-01 00:00:00
abstract::Freeze-fracture and thin-section electron microscopy and morphometry were used to characterize further the response of the rat medullary collecting duct to potassium depletion. In freeze-fracture replicas, principal cells and intercalated cells were identified based on the assumption that intercalated cells possess a ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.6
更新日期:1980-01-01 00:00:00
abstract::The importance of the endothelial isoform of nitric oxide synthase (eNOS) has been well established. Endothelium-derived nitric oxide has been shown to be essential for vascular homeostasis and modulation of eNOS has thus become a target in prevention of cardiovascular disease. The role of the inducible form of nitric...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1046/j.1523-1755.2002.00235.x
更新日期:2002-03-01 00:00:00
abstract:BACKGROUND:The hypothesis that angiotensin-converting enzyme (ACE) inhibitors interfere with the treatment of anemia with recombinant human erythropoietin (rHuEPO) remains controversial. To test this hypothesis, a retrospective analysis was conducted in a large group of hemodialysis patients with renal anemia. METHODS...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00028.x
更新日期:2001-11-01 00:00:00
abstract::This study offers morphological evidence of the involvement of lipid abnormalities in human glomerular injury. Renal biopsy tissues from patients with several types of glomerular diseases were immunocytochemically examined using antibodies to apolipoproteins (apo) A-I, B-100, and E, and antibodies to low density lipop...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.129
更新日期:1993-04-01 00:00:00
abstract::Quartan malarial infection causes an immune complex nephritis in some individuals, which, once established, is sustained by mechanisms not yet fully explained, but which probably involve autoimmune processes. The presenting clinical and biochemical findings of the quartan malarial nephrotic syndrome are similar to tho...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1979.103
更新日期:1979-07-01 00:00:00
abstract::Tubulointerstitial fibrosis is one of the most important histologic features that predicts progression in kidney disease. Thrombospondin 1 is an extracellular matrix protein that can activate latent TGF-beta, a cytokine implicated in the pathogenesis of tubulointerstitial fibrosis. We examined the expression of thromb...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00774.x
更新日期:1998-02-01 00:00:00
abstract::Membranous nephropathy is a major cause of nephrotic syndrome in adults where podocyte injuries were found to mediate the development of proteinuria. Triptolide, a major active component of Tripterygium wilfordii Hook F, has potent immunosuppressive, anti-inflammatory and antiproteinuric effects. To study its antiprot...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.41
更新日期:2010-06-01 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::Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase. Its activation results in beneficial or detrimental consequences, depending on the particular setting. Earlier studies in the animal model of acute kidney injury showed that EGFR activation promotes renal tubular cell proliferation. Activation of E...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2012.435
更新日期:2013-05-01 00:00:00
abstract::A strong influence of urinary kallikrein excretion on the salt sensitivity of blood pressure has been recently suggested in normotensive patients. To evaluate the relationship between kallikrein and salt sensitivity in essential hypertension, active kallikrein excretion, plasma renin activity, atrial natriuretic pepti...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1994.333
更新日期:1994-09-01 00:00:00
abstract::Autologous and allogeneic bone marrow grafting both require cytoreductive therapy but only the allogeneic procedure requires immunosuppressive agents. Allogeneic bone marrow transplantation has been reported to be associated with a high incidence of both renal failure and veno-occlusive disease (VOD) of the liver, the...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1996.405
更新日期:1996-09-01 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::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::The binding of albumin to the glomerular capillary wall was studied using albumin-gold in perfused kidneys, the interaction of [3H]albumin with isolated glomeruli at 37 degrees C and 4 degrees C and the interaction at [3H]albumin with purified basement membrane. The albumin-gold was found to bind predominantly to the ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.149
更新日期:1995-04-01 00:00:00
abstract:BACKGROUND:Caveolin is a principal component of caveolae and regulates signaling in caveolae. Mesangial cells contain many caveolae, and thus manipulation of caveolin-1 expression level might be useful to control mesangial cell proliferation, which is an important aggravating factor in many renal diseases. METHODS:In ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00954.x
更新日期:2004-11-01 00:00:00
abstract::Parathyroid suppression by intraperitoneal calcitriol (1,25(OH)2D3) during peritoneal dialysis. The purpose of this study was to determine if parathyroid hormone (PTH) suppression could be achieved by increasing calcium mass transfer (Ca MT) with high dialysate Ca (4 mEq/liter) or via intraperitoneal (i.p.) 1,25(OH)2D...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1987-03-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00027.x
更新日期:1998-08-01 00:00:00
abstract::Chemotherapy-induced nephrotoxicity limits the success of cancer therapy. Landau et al. now describe a mechanism by which a first dose of cisplatin renders the kidney sensitive to necroptosis mediated by a second dose. Unresolved injury and sustained necrosis, therefore, may represent a pathophysiological means of tra...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2018.12.004
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:We have recently demonstrated an increase in apoptosis in Han:SPRD rat kidneys with autosomal-dominant polycystic kidney disease (ADPKD). Caspase-3 and caspase-7 are major mediators of apoptosis. There are two pathways of caspase-3 and caspase-7-mediated apoptosis: (1) the "extrinsic" pathway involving the d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00155.x
更新日期:2005-03-01 00:00:00
abstract::Cytokines are important modulators of inflammation. The balance between pro- and anti-inflammatory cytokines determines whether the intensity of inflammatory response is within physiological limits or in the pathological range. The cytokine network is highly complex, containing interactive cascades of gene activation ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002391
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:Recent advances enable the direct measurement of small molecule clearance, Kecn, during each dialysis. Average Kecn and treatment length, t, are multiplied giving total clearance, Kt. The body surface area (BSA) is a fixed transformation of height and weight and is a well recognized measure of body size. Thi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00533.x
更新日期:2005-09-01 00:00:00
abstract::Intestinal regulation of oxalate absorption is a complex mechanism, not exclusively reliant on the oxalate-degrading anaerobe Oxalobacter formigenes. Using metagenomics, Miller et al. were able to describe a network of bacterial taxa co-occurring with Oxalobacter formigenes in fecal samples from non-stone forming cont...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2019.03.020
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:Atherogenic lipoproteins cause injury to the vascular wall in the early phase of atherogenesis. We assessed the effects of native (nLDL) and oxidized (oxLDL) low-density lipoprotein (LDL) and lipoprotein (a) [Lp(a)] on O2- formation and cell death in cultured human umbilical vein endothelial cells (HUVECs) a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00351.x
更新日期:1999-04-01 00:00:00
abstract:BACKGROUND:The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with end-stage renal disease (ESRD). Adiponectin is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00370.x
更新日期:2004-01-01 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::This NIH-funded multicenter randomized study of focal segmental glomerulosclerosis (FSGS) treatment compared the efficacy of a 12-month course of cyclosporine to a combination of oral pulse dexamethasone and mycophenolate mofetil in children and adults with steroid-resistant primary FSGS. Of the 192 patients enrolled,...
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.2011.195
更新日期:2011-10-01 00:00:00