Abstract:
BACKGROUND:Endotoxin is an important factor in the development of acute renal failure related to infection and in acceleration of chronic nephritis. Lipopolysaccharide (LPS; the major component of endotoxin) is one of the most potent triggers for renal cells to produce monocyte chemoattractant protein-1 (MCP-1), a key cytokine involved in immune cell recruitment into the renal interstitium in acute and chronic renal diseases. Knowledge about the transcriptional regulation of MCP-1 in renal tubular epithelial cells in response to LPS is incomplete. METHODS:Transcriptional regulation of MCP-1 was investigated in rat proximal tubule cells (PTCs) in primary culture and was exposed to LPS using electromobility shift assay and supershift analysis for nuclear factor-kappaB (NF-kappaB) and Western blot for the NF-kappaB inhibitory protein IkappaB. To prove the role for NF-kappaB, activator protein (AP-1), and sequence-specific transcription factor (Sp1), mutation and deletion analysis was performed using a 3.5 kb fragment of rat MCP-1 5'-flanking region inserted into a luciferase reporter construct transfected into tubular epithelial cell line (NRK-52E). RESULTS:LPS increased NF-kappaB in a dose- and time-dependent manner, which paralleled that of MCP-1 mRNA expression. IkappaBalpha decreased within 30 minutes of LPS treatment, but returned to basal levels by two hours. IkappaBbeta levels were depressed within one hour and remained low throughout the culture period after LPS stimulation. The activity of the transfected 5'-flanking region of the MCP-1 gene increased nearly threefold after LPS stimulation. Mutation or deletion of NF-kappaB binding sites, located in the enhancer region of the 5'-flanking region, resulted in a total loss of LPS-induced increase in luciferase activity. Mutation of putative AP-1 and Sp1 sites, located in the proximal promoter region of MCP-1, reduced basal luciferase activity in unstimulated cells, but had no effect on LPS-stimulated luciferase activity. CONCLUSIONS:These studies prove that NF-kappaB is critical for LPS-induced MCP-1 transcription, and AP-1 and Sp1 are essential for basal expression of MCP-1 in rat tubule cells. The species-specific nature of transcriptional regulation of MCP-1 has important implications for the delineation of treatment to prevent endotoxin-mediated renal injury.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Wang Y,Rangan GK,Goodwin B,Tay YC,Harris DCdoi
10.1046/j.1523-1755.2000.00051.xsubject
Has Abstractpub_date
2000-05-01 00:00:00pages
2011-22issue
5eissn
0085-2538issn
1523-1755pii
S0085-2538(15)46953-4journal_volume
57pub_type
杂志文章abstract::IgG4-related disease is a recently recognized multi-organ disorder characterized by high levels of serum IgG4 and dense infiltration of IgG4-positive cells into several organs. Although the pancreas was the first organ recognized to be affected by IgG4-related disorder in the syndrome of autoimmune pancreatitis, we pr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.271
更新日期:2010-11-01 00:00:00
abstract::Only some individuals carrying the high-risk APOL1 genotype go on to develop kidney disease phenotypes. In this issue of Kidney International, Nadkarni and colleagues report the associations of several biomarkers with renal outcomes in individuals with high-risk APOL1 genotypes. In the era of precision medicine, these...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2018.03.005
更新日期:2018-06-01 00:00:00
abstract::Lithium therapy frequently induces nephrogenic diabetes insipidus; amiloride appears to prevent its occurrence in some clinical cases. Amiloride blocks the epithelial sodium channel (ENaC) located in the apical membrane of principal cells; hence one possibility is that ENaC is the main entry site for lithium and the b...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.91
更新日期:2009-07-01 00:00:00
abstract:BACKGROUND:Unilateral ureteral obstruction (UUO) leads to interstitial fibrosis of the obstructed kidney, and TGF-beta is considered to play an important role in this fibrotic process. Smad7 has been recently identified as an antagonist of TGF-beta signaling. To investigate whether this novel molecule can be exploited ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.0610s1094.x
更新日期:2002-01-01 00:00:00
abstract::Nephropathy is among the most frequent complications of diabetes and the leading cause of end-stage renal disease. Despite the success of novel drugs in animal models, the majority of the subsequent clinical trials employing those drugs targeting diabetic nephropathy failed. This lack of translational value may in par...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.06.023
更新日期:2016-11-01 00:00:00
abstract::The molecular mechanism of Na+ and phosphate transport by the intestinal brush border membrane Na+/phosphate cotransporter was examined using anion and cation exchange columns interfaced to a light-activated microsecond timer. The nature of ion:cotransporter interaction was examined for sensitivity to itself versus no...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.141
更新日期:1996-04-01 00:00:00
abstract::Incretin-based drugs, i.e., glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are widely used for the treatment of type 2 diabetes. In addition to the primary role of incretins in stimulating insulin secretion from pancreatic β-cells, they have extra pancreatic functions ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2014.236
更新日期:2014-10-01 00:00:00
abstract::The acutely injured mammalian kidney mounts a cellular and molecular response to repair itself. However, in patchy regions such intrinsic processes are impaired and dysregulated leading to chronic kidney disease. Currently, no therapy exists to treat established acute kidney injury per se. Strategies to augment human ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2017.07.030
更新日期:2018-01-01 00:00:00
abstract::Methods for estimating glomerular volume were compared in Zenker-fixed, paraffin-embedded biopsies from 10 patients with insulin-dependent diabetes mellitus and 6 normal kidney donors. Two methods of measurement of individual glomerular volumes were used: the Cavalieri method (considered the "gold standard") and the m...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.165
更新日期:1992-04-01 00:00:00
abstract::Autophagy is a dynamic and highly regulated process of self-digestion responsible for cell survival and reaction to oxidative stress. As oxidative stress is increased in uremia and is associated with vascular calcification, we studied the role of autophagy in vascular calcification induced by phosphate. In an in vitro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.482
更新日期:2013-06-01 00:00:00
abstract::It is well known that uremia causes an increase in the serum anion gap (AG); however, whether changes in the AG occur earlier in the course of chronic kidney disease is not known. Here we investigated whether different measures of the AG, as a marker of kidney function, are associated with mortality. To do this, we an...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.196
更新日期:2012-09-01 00:00:00
abstract::Pathogenesis of vascular calcification in chronic kidney disease. Background. Hyperphosphatemia and hypercalcemia are independent risk factors for higher incidence of cardiovascular events in patients with chronic kidney disease. In addition to increased calcium-phosphate product, hyperphosphatemia accelerates the pro...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1111/j.1523-1755.2005.00421.x
更新日期:2005-08-01 00:00:00
abstract::A genome-wide association study (GWAS) indicated that myeloperoxidase-ANCA associated vasculitis (AAV) is associated with HLA-DQ. However, susceptibility alleles in these loci have been under-investigated. Here we genotyped 258 Chinese patients with myeloperoxidase-AAV and 597 healthy control individuals at HLA DRB1, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.06.015
更新日期:2019-10-01 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::Pulse wave velocity (PWV) was measured in the aorta, right leg and arm of 90 control subjects (CS) and 92 hemodialysis patients (HD) of the same age and mean arterial pressure (MAP). Blood chemistry, including blood lipids, and echographic dimensions of the aorta, were measured in all subjects. Presence of aortic calc...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.19
更新日期:1990-01-01 00:00:00
abstract::The intracellular distribution of carbonic anhydrase was studied in nine human donor kidneys by the histochemical method of Hansson and by an immunofluorescence technique using antisera specific against the cytoplasmic isoenzymes HCA B and HCA C. Only HCA C was found in the renal tubules. Convoluted proximal tubules s...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.106
更新日期:1984-06-01 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::Proteinuric diabetic patients have an increased risk of cardiovascular disease and almost always have hypertension. In the early stages of diabetic renal disease (microalbuminuria) when renal function is well preserved, systemic arterial blood pressure is already elevated compared to insulin-dependent diabetic patient...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1994.56
更新日期:1994-02-01 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 next phase of the molecular revolution will bring functional genomics down to the level of individual cells in a tissue. Laser capture microdissection (LCM) coupled with reverse transcription-polymerase chain reaction (RT-PCR) can measure gene expression in normal, cancerous, injured, or fibrotic tissue....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00295.x
更新日期:2000-09-01 00:00:00
abstract::Long-term complications of continuous immunosuppression still remain a serious threat and are currently drawing the attention of transplant physicians. Wimmer et al. show that malignancy occurs approximately fourfold more frequently in renal-transplant recipients than in a normal control population. Besides immunosupp...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002306
更新日期:2007-06-01 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::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::When patients develop acute kidney injury, a small fraction of them will develop end-stage renal disease later. The severity of renal impairment in the remaining patients is uncertain because studies have not carefully examined renal function over time or the precise timing of entry into a late stage of chronic kidney...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.332
更新日期:2009-11-01 00:00:00
abstract::A controlled trial of cyclosporine in patients diagnosed with progressive membranous nephropathy (MGN) was carried out to determine whether cyclosporine (D) would be more effective than placebo (P) in reducing the rate of deterioration in renal function. Patients (N = 64) with MGN were placed on a restricted protein d...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1995.161
更新日期:1995-04-01 00:00:00
abstract::Acute phosphate nephropathy (APhN) is a clinical pathological entity characterized by acute and subsequent chronic renal failure following exposure to oral sodium phosphate (OSP) bowel purgatives. Renal biopsy findings include acute and chronic tubular injury with prominent tubular and interstitial calcium phosphate d...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2009.308
更新日期:2009-11-01 00:00:00
abstract:BACKGROUND:Heparins are currently the anticoagulants of choice in long-term hemodialysis (HD). Because of their shortcomings, including the increasing incidence of heparin-induced thrombocytopenia (HIT II), alternative anticoagulation is necessary. The study objectives were to provide safe and effective HD by investiga...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1111/j.1523-1755.2004.00433.x
更新日期:2004-02-01 00:00:00
abstract::One of the challenges of treating patients with glomerulonephritis is to accurately assess disease activity. As renal biopsies are routinely stained for deposits of C3 activation fragments and glomerular C3 deposits are found in most forms of glomerulonephritis, we sought to determine whether a relatively noninvasive ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.332
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:The alteration of renal cell growth is one of the early abnormalities in the diabetic nephropathy. However, the effects of high glucose and its action mechanism in renal proximal tubule cell (PTC) proliferation have not been elucidated. METHODS:The effects of 25 mmol/L glucose on cell proliferation, thymidi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590051695.x
更新日期:2001-05-01 00:00:00
abstract::Residual renal function is a major survival determinant for peritoneal dialysis patients. Hypovolemia can cause acute kidney injury and loss of residual renal function, and it has been suggested that patients receiving peritoneal dialysis should preferably be maintained hypervolemic to preserve residual renal function...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.273
更新日期:2014-01-01 00:00:00