Abstract:
BACKGROUND:The renin-angiotensin system has been known to regulate blood pressure and body fluid homeostasis. Several lines of evidence have shown that renin gene expression and release are up-regulated by beta-adrenergic stimulation, sodium depletion, and angiotensin converting enzyme inhibition, but down-regulated by cytokines. To further characterize the human renin gene (hREN) promoter structure, its regulation, and to identify an appropriate cell system for study, we examined five cell lines and investigated drug effects on the hREN promoter expression. METHODS:Using the hREN-luciferase reporter gene constructs in the DNA transfection assays, approximately 5 kb of the hREN 5' flanking region was assessed for promoter activity in five different cell lines. Regulation of the hREN promoter activity was investigated using Y-1 adrenal cells that were transfected with the hREN-luciferase DNA and were treated with forskolin, calcium ionophore A23187, phorbol ester, angiotensin II (Ang II), or cytokines. RESULTS:Transient transfection analysis showed that the 5 kb hREN 5' flanking DNA alone was able to confer significant promoter activity in Y-1 adrenal cells. In transfected Y-1 cells, luciferase reporter expression was induced by forskolin, suppressed by the calcium ionophore A23187, and phorbol ester in a dose-dependent manner, but was unaffected by angiotensin II (Ang II). However, when Y-1 reporter cells were transfected with human angiotensin II receptor type 1 (AT1) cDNA, hREN promoter activity was dose-dependently down-regulated by Ang II, which was blockable by losartan, an AT1-selective antagonist. Further studies also showed that hREN promoter activity in Y-1 cells was selectively down-regulated by TNF alpha. Deletion of the hREN promoter sequences between position -3916 and -2822 not only enhanced hREN promoter activity by approximately tenfold, but also caused a failure of down-regulation by TNF alpha. In contrast, neither interleukin (IL)-1 alpha, IL-1 beta, IL-2, nor IL-6 exerted any significant effect. CONCLUSIONS:Together the results suggest that TNF alpha is a negative regulator of the hREN expression in the adrenal cells, and that the TNF alpha responsiveness may be controlled by elements located between the positions -3916 and -2822 of the hREN promoter. Moreover, the Y-1 cell line may provide a valuable model system for studying renin gene regulation.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Chen LS,Cuddy MP,LaVallette LAdoi
10.1046/j.1523-1755.1998.00209.xsubject
Has Abstractpub_date
1998-12-01 00:00:00pages
2045-55issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(15)30842-5journal_volume
54pub_type
杂志文章abstract::Reducing proteinuria and blood pressure in chronic kidney disease (CKD) decreases rate of progression. Inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers is beneficial in reducing proteinuria but incomplete in suppressing aldosterone production a...
journal_title:Kidney international
pub_type: 评论,杂志文章,评审
doi:10.1038/sj.ki.5002007
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND:Although apoptosis has been linked to the renal cell deletion and ensuing renal fibrosis, its regulating mechanisms remain obscure. Of the known regulators of apoptosis, the best characterized is the Bax to Bcl-2 ratio. However, its importance in controlling apoptosis in glomerulonephritis is unclear. Here, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2002.kid587.x
更新日期:2002-10-01 00:00:00
abstract:BACKGROUND:Susceptibility to skin cancer after transplantation is multifactorial, and risk factors include skin type, sun exposure, and level of immunosuppression. A major mechanism of carcinogenesis is ultraviolet radiation-induced free radical damage, and genetically determined ability to metabolize free radicals may...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2000.00392.x
更新日期:2000-11-01 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:BACKGROUND:Neointimal hyperplasia occurs commonly at the anastomoses of arteriovenous grafts for chronic hemodialysis, causing stenosis and occlusion. Antiproliferative drugs may be effective in inhibiting hyperplasia, but local drug delivery would be required to minimize systemic side effects. We examined the feasibil...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00985.x
更新日期:2004-11-01 00:00:00
abstract::[Arg(8)]-vasopressin (AVP) has several functions via its three distinct receptors, V1a, V1b, and V2. The V1a vasopressin receptor (V1aR) is expressed in blood vessels and involved in vascular contraction. Recently, we generated V1a receptor-deficient (V1aR(-/-)) mice and found that they were hypotensive. In addition, ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2009.319
更新日期:2009-11-01 00:00:00
abstract::Superoxide (O2-) production and Fc alpha R antigen expression of circulating polymorphonuclear leukocytes (PMNL) isolated from patients with IgA nephropathy (IgAN) and non-IgA mesangial proliferative glomerulonephritis (PGN) and healthy volunteers were investigated to establish their biological importance in the immun...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.114
更新日期:1994-03-01 00:00:00
abstract::A new study by Xu et al. presents compelling evidence for an important role of the glomerular endothelium in acute kidney injury. They show that lipopolysaccharide reduces the endothelial surface layer, resulting in mild albuminuria, reduced glomerular filtration rate, and fewer endothelial fenestrae. Tumor necrosis f...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.317
更新日期:2014-01-01 00:00:00
abstract::IgA nephropathy (IgAN) often shows lesions morphologically identical with those of focal segmental glomerulosclerosis (FSGS). In order to determine the possible role of FSGS in IgAN lesions, we measured glomerular capsular adhesions, often the first step toward FSGS, in biopsies from 127 patients with IgAN, 100 with l...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.466
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy (RRT), concerns remain regarding the bioincompatible nature of standard PD fluid. In order to evaluate whether a newly formulated fluid of neutral pH, and containing low levels of glucose degradation products (GDP), resu...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1111/j.1523-1755.2004.00747.x
更新日期:2004-07-01 00:00:00
abstract::Mice chronically infected with the virus of lymphocytic choriomeningitis (LCM) develop immune complex glomerulonephritis. Others have shown that adoptive immunization of these mice by the i.p. injection of syngeneic immune spleen cells terminates the chronic viral carrier state. The present studies were designed to de...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.49
更新日期:1977-05-01 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
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::Primary hyperoxaluria is characterized by severe urolithiasis, nephrocalcinosis, and early renal failure. As treatment options are scarce, we aimed for a new therapeutic tool using colonic degradation of endogenous oxalate by Oxalobactor formigenes. Oxalobacter was orally administered for 4 weeks as frozen paste (IxOC...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/sj.ki.5001707
更新日期:2006-10-01 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::beta 2-microglobulin-related amyloidosis (A beta 2M) represents a frequent complication in long-term dialysis patients. Although the pathogenetic mechanism has yet to be fully understood, it is known that amyloid fibrils usually consist of intact molecules of beta 2-microglobulin (beta 2m). Plasma proteinase inhibitor...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.368
更新日期:1992-10-01 00:00:00
abstract::In this mini review, we would like to challenge the well-established 'fact' that lead exposure causes chronic renal failure (CRF). Even though only scarce evidence exists of the relationship between lead and renal failure, a World Health Organization Environmental Health Criteria document summarizes that 'Lead has bee...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2010.394
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND:Renal disease is commonly associated with hyperlipidemia and correlates with glomerular accumulation of atherogenic lipoproteins, for example, lipoprotein(a) [Lp(a)], and mesangial hypercellularity. Specific binding of Lp(a) to mesangial cells and induction of c-myc and c-fos expression has been demonstrated...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00367.x
更新日期:1999-04-01 00:00:00
abstract::Previous studies have shown that nonsteroidal anti-inflammatory drug (NSAID) use might be associated with a lower risk of developing cancer in the general population. Patients on dialysis have increased risk for cancer, but there are no studies to determine the relationship between NSAID use and cancer risk in these p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.79
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:The characteristic feature of Goodpasture disease is the occurrence of an autoantibody response to the noncollagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] in the alveolar and glomerular basement membrane. These antibodies are associated with the development of a rapidly progressive ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.055003936.x
更新日期:1999-03-01 00:00:00
abstract::We reviewed the diagnostic features and clinical course of 140 patients with idiopathic membranous nephropathy who had their index renal biopsies performed at the Mayo Clinic between 1972 and 1984. There were 93 males and 47 females (average age, 50.8 +/- 17 years); 116 patients (83%) had the nephrotic syndrome and 42...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.56
更新日期:1988-03-01 00:00:00
abstract::For reasons that are not well understood, Aboriginal people with end-stage renal disease (ESRD) have lower rates of kidney transplantation. We hypothesized that distance between residence location and the closest transplant center was greater in Aboriginal dialysis patients and would partially explain the lower rate o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001607
更新日期:2006-09-01 00:00:00
abstract::The remnant kidney model was produced in mice by unilateral nephrectomy and partial infarction of the remaining kidney. Control mice underwent laparotomy only. The mice were studied for up to 44 weeks. No quantitative differences were noted in systolic arterial pressure, proteinuria, or histopathology between control ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00527.x
更新日期:1999-07-01 00:00:00
abstract::Cyanate is a uremic toxin responsible for the carbamylation of proteins, which has been implicated as playing a key role in accelerating the progression of atherosclerosis in patients with chronic kidney disease. El-Gamal et al. report that while cyanate promotes protein carbamylation in vivo, the resulting endothelia...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.256
更新日期:2014-11-01 00:00:00
abstract::Although the goal glomerular filtration rate (GFR) for chronic dialysis initiation is currently above 5 ml/min per 1.73 m(2), there is no convincing evidence that patients will benefit from this approach. With close follow-up of advanced chronic kidney disease patients, aiming to start dialysis at an estimated GFR (eG...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.164
更新日期:2014-10-01 00:00:00
abstract::The increasing use of mice in renal and cardiovascular studies has necessitated adapting physiological methods used for rats to mice, which are far smaller in size. We have adapted measurements of continuous renal blood flow, pressure natriuresis and diuresis, and laser-Doppler cortical and medullary flow to 40 g mice...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.462
更新日期:1997-11-01 00:00:00
abstract:BACKGROUND:The beneficial effect of blood transfusions before cadaveric renal transplantation on allograft survival, although previously well documented, has become controversial in light of their adverse effects. Recently, it has been suggested that their clinical benefits are due to HLA-DR sharing between the blood d...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1046/j.1523-1755.2001.00805.x
更新日期:2001-07-01 00:00:00
abstract::Gap junctions are present in the juxtaglomerular apparatus enabling intercellular communication. Our study determined the location of different connexin subtypes within the juxtaglomerular apparatus of the rat, and the role of these subtypes in renal hemodynamics through the use of specific mimetic peptides. Immunohis...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002673
更新日期:2008-02-01 00:00:00
abstract::The antiproteinuric effect of angiotensin converting enzyme (ACE) inhibition in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy varies considerably. Therefore, we tested the potential role of an insertion (I)/deletion (D) polymorphism of the ACE gene on this early antiproteinuric responsi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.1998.00847.x
更新日期:1998-04-01 00:00:00
abstract::The Institute of Medicine's recent report, Organ Donation: Opportunities for Action, studies the current problems facing organ donation in the USA, making suggestions for quality improvement and analyzing various proposals of incentivized donation and presumed consent (PC). Although the report deals with the donation ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002143
更新日期:2007-04-01 00:00:00