Abstract:
:Inflammatory responses in the kidney lead to tubulointerstitial fibrosis, a common feature of chronic kidney diseases. Here we examined the role of prostaglandin E(2) (PGE(2)) in the development of tubulointerstitial fibrosis. In the kidneys of wild-type mice, unilateral ureteral obstruction leads to progressive tubulointerstitial fibrosis with macrophage infiltration and myofibroblast proliferation. This was accompanied by an upregulation of COX-2 and PGE(2) receptor subtype EP(4) mRNAs. In the kidneys of EP(4) gene knockout mice, however, obstruction-induced histological alterations were significantly augmented. In contrast, an EP(4)-specific agonist significantly attenuated these alterations in the kidneys of wild-type mice. The mRNAs for macrophage chemokines and profibrotic growth factors were upregulated in the kidneys of wild-type mice after ureteral obstruction. This was significantly augmented in the kidneys of EP(4)-knockout mice and suppressed by the EP(4) agonist but only in the kidneys of wild-type mice. Notably, COX-2 and MCP-1 proteins, as well as EP(4) mRNA, were localized in renal tubular epithelial cells after ureteral obstruction. In cultured renal fibroblasts, another EP(4)-specific agonist significantly inhibited PDGF-induced proliferation and profibrotic connective tissue growth factor production. Hence, an endogenous PGE(2)-EP(4) system in the tubular epithelium limits the development of tubulointerstitial fibrosis by suppressing inflammatory responses.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Nakagawa N,Yuhki K,Kawabe J,Fujino T,Takahata O,Kabara M,Abe K,Kojima F,Kashiwagi H,Hasebe N,Kikuchi K,Sugimoto Y,Narumiya S,Ushikubi Fdoi
10.1038/ki.2012.115subject
Has Abstractpub_date
2012-07-01 00:00:00pages
158-71issue
2eissn
0085-2538issn
1523-1755pii
S0085-2538(15)55510-5journal_volume
82pub_type
杂志文章abstract::The effects of acidosis on renal function and morphology were examined in the isolated perfused rat kidney (IPK). Kidneys were perfused with oxygenated Krebs-Henseleit-albumin medium for 60 minutes at pH 7.4 or pH 7.0. At the lower pH, GFR was reduced by 25%, TRNa by 32% and oxygen consumption by 41% as compared to pe...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.251
更新日期:1988-12-01 00:00:00
abstract:BACKGROUND:Alterations of large artery function and structure are frequently observed in renal allograft recipients. However, endothelial function has not yet been assessed in this population. METHODS:Flow-mediated vasodilation is a useful index of endothelial function. We measured the diameter and distensibility of t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.0550031104.x
更新日期:1999-03-01 00:00:00
abstract::Kinetic parameters were studied to determine the effectiveness of hemoperfusion in removing ethychlorvynol from the plasma and red blood cells (RBC) of intoxicated dogs. Perfusion columns contained polystyrene/divinyl benzene resin (XAD-4 Amberlite. Column clearances of ethchlorvynol averaged 96.5 +/- 0.4% of the plas...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.36
更新日期:1980-03-01 00:00:00
abstract:BACKGROUND:Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the development of ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the effects of a water-soluble and potent PARP inhibitor, 5-aminoisoquinolinone (5-AIQ), on the re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00415.x
更新日期:2004-02-01 00:00:00
abstract:BACKGROUND:Although atherosclerotic renovascular disease is increasingly recognized in chronic kidney disease, few national level studies have examined its clinical epidemiology. METHODS:Claims data from a 5% random sample of the United States Medicare population were used to select patients without atherosclerotic re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00406.x
更新日期:2005-07-01 00:00:00
abstract::The generation of reactive oxygen species has a pivotal role in both acute and chronic glomerular injuries in patients with lupus nephritis. As the transcription factor Nrf2 is a major regulator of the antioxidant response and is a primary cellular defense mechanism, we sought to determine a role of Nrf2 in the progre...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.343
更新日期:2014-02-01 00:00:00
abstract::The current study was undertaken to examine the effects of dithiothreitol (DDT), a sulfhydryl-reducing agent and heavy metal chelator, on the course of heavy metal-induced acute renal failure in the rat. Groups of rats in metabolic cages received uranyl nitrate (UN) alone, UN plus DTT, mercuric chloride (HgCl2) alone,...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.88
更新日期:1977-08-01 00:00:00
abstract::Experimental studies have demonstrated the cardinal role played by the mononuclear phagocyte system in the removal of antigen-antibody complexes. To assess the functional capacity of phagocytes in patients with renal disease, 33 normal subjects, 10 patients with mesangial proliferative glomerulonephritis, 8 patients w...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.105
更新日期:1983-06-01 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::Spontaneous polycystic kidney and liver disease in an inbred herd of Springbok (Antidorcas marsupialis) was studied by light microscopy, transmission electron microscopy, and microdissection. Springbok are a small species of gazelle of the family Bovidae native to South Africa. Since 1976, 18% of all live calves born ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.146
更新日期:1982-08-01 00:00:00
abstract:BACKGROUND:Strict glycemic control and antihypertensive treatment may decrease but not eliminate the risk of progressive nephropathy in diabetic patients. C-peptide has been shown to exert beneficial effects on complications, including incipient nephropathy, in type 1 diabetes. METHODS:Renal effects of 14 days of intr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00964.x
更新日期:2001-10-01 00:00:00
abstract:BACKGROUND:Patients on continuous ambulatory peritoneal dialysis (CAPD) are dependent on residual renal function for solute and water clearances, and this declines with time on dialysis. Loop diuretics have been postulated to slow this decline. METHODS:Sixty-one patients new to dialysis were randomly assigned to eithe...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1523-1755.2001.0590031128.x
更新日期:2001-03-01 00:00:00
abstract::Low density lipoprotein (LDL) deposition and local oxidation play a key role in the pathogenesis of atherosclerosis and may likewise contribute to glomerular injury. These studies were designed to determine whether cultured human mesangial cells oxidize homologous LDL and to compare the effects of unmodified and oxidi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.214
更新日期:1994-06-01 00:00:00
abstract:BACKGROUND:While the progression of renal disease to end stage is strongly correlated with tubulointerstitial changes, the control of the fibrotic process within the interstitium is poorly understood. Basic fibroblast growth factor (FGF-2) has been implicated as a major growth factor involved in fibroblast activation a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00723.x
更新日期:2001-06-01 00:00:00
abstract::A major factor contributing to failure of arteriovenous fistulas (AVFs) is migration of smooth muscle cells into the forming neointima. To identify the source of smooth muscle cells in neointima, we created end-to-end AVFs by anastomosing the common carotid artery to the jugular vein and studied neural crest-derived s...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.73
更新日期:2015-09-01 00:00:00
abstract::Alport syndrome is experiencing a remarkable increase in preclinical investigations. To proactively address the needs of the Alport syndrome community, as well as offer clarity for future clinical research sponsors, the Alport Syndrome Foundation hosted a workshop to generate consensus recommendations for prospective ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.02.029
更新日期:2020-06-01 00:00:00
abstract::The influence of transforming growth factor beta 1 (TGF-beta 1) and of dexamethasone on fibronectin (FN) synthesis of human renal tubular epithelial cells in culture (TEC) was studied. Cocultivation with TGF-beta 1 increased the steady state level of FN RNA within 24 to 48 hours. By PCR and Northern blotting it was fo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.479
更新日期:1995-12-01 00:00:00
abstract::Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible 14 (TWEAK-Fn14), are widely expressed and are involved in both injury and repair. Hotta et al. now demonstrate an important role for Fn14 in the common clamp ischemia model of acute kidney injury. Their da...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2010.435
更新日期:2011-01-01 00:00:00
abstract::Bikunin is a chondroitin-sulphate containing serum protein with a Stokes-Einstein radius and a negative net charge close to those of serum albumin. The plasma half life of bikunin is about 10 minutes, and approximately half of its clearance occurs in the kidneys. The quantitative role of glomerular filtration in the r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.147
更新日期:1997-04-01 00:00:00
abstract::A recent clinical trial in patients with chronic kidney disease (CKD) and diabetic nephropathy demonstrated that bardoxolone methyl (CDDO-ME) increases estimated glomerular filtration rate (eGFR) by an unknown mechanism. The paper by Ding et al. suggests that short-term administration of a CDDO-ME analog increases GFR...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.38
更新日期:2013-05-01 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::As the worldwide prevalence of end-stage renal disease increases it is important to evaluate the rate of living kidney donation in various countries; however there is no comprehensive global assessment of these rates. To measure this, we compiled data from representatives, renal registries, transplant networks, publis...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.20
更新日期:2009-05-01 00:00:00
abstract::The relative importance of sarcopenia and its individual components as independent predictors of mortality in the dialysis population has not been determined. We estimated whole-body muscle mass using pre-dialysis bioimpedance spectroscopy measurements in 645 ACTIVE/ADIPOSE-enrolled prevalent hemodialysis patients fro...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2017.01.024
更新日期:2017-07-01 00:00:00
abstract:BACKGROUND:The p21 protein is found in the nucleus of most cells where it modulates cell cycle activity. At low levels, p21 stabilizes interactions between D cyclins and their cyclin-dependent kinases (cdks), but at high levels after induction by several different stress pathways, it causes cell cycle arrest. The p21 m...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00044.x
更新日期:2001-12-01 00:00:00
abstract::The purpose of this prospective, angiographically controlled study was to determine the diagnostic value of color Doppler sonography with two differing approaches of scanning in patients with clinical clues for renal artery stenosis (RAS). In 135 hypertensive patients peak systolic velocity in the main renal arteries ...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1996.440
更新日期:1996-10-01 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 present experiments were performed to examine the effect of variation in protein intake on renal function and morphology in the non-clipped kidneys of Goldblatt hypertensive rats. After renal artery clipping, rats were put on diets containing 5 (LP), 17.5 (NP), or 51% (HP) protein. After 4 to 5 weeks, all rats had...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.30
更新日期:1986-02-01 00:00:00
abstract::Genetic deletion of the adenosine A1 receptor (A1AR) increased renal injury following ischemia-reperfusion injury suggesting that receptor activation is protective in vivo. Here we tested this hypothesis by expressing the human-A(1)AR in A(1)AR knockout mice. Renal ischemia-reperfusion was induced in knockout mice 2 d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.699
更新日期:2009-04-01 00:00:00
abstract::A major contributor to the development and progression of ischemia-reperfusion (IR)-induced acute renal failure (ARF) is the loss of functioning tubular epithelial cells by means of various cell deletion or death processes. Although the term "acute tubular necrosis" is still used to describe the pathology of ARF, this...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00701.x
更新日期:1999-10-01 00:00:00
abstract:BACKGROUND:Human immunodeficiency virus-associated nephropathy (HIVAN) has become the third leading cause of end-stage renal disease (ESRD) in African Americans, and is expected to grow exponentially. Highly active antiretroviral therapy (HAART) has significantly prolonged the survival of patients with HIV infection. D...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00245.x
更新日期:2005-04-01 00:00:00