Abstract：
:Lysophosphatidic acid (LPA) is known to regulate various biological responses by binding to LPA receptors. The serum level of LPA is elevated in diabetes, but the involvement of LPA in the development of diabetes and its complications remains unknown. Therefore, we studied LPA signaling in diabetic nephropathy and the molecular mechanisms involved. The expression of autotaxin, an LPA synthesis enzyme, and LPA receptor 1 was significantly increased in both mesangial cells (SV40 MES13) maintained in high-glucose media and the kidney cortex of diabetic db/db mice. Increased urinary albumin excretion, increased glomerular tuft area and volume, and mesangial matrix expansion were observed in db/db mice and reduced by treatment with ki16425, a LPA receptor 1/3 antagonist. Transforming growth factor (TGF)β expression and Smad-2/3 phosphorylation were upregulated in SV40 MES13 cells by LPA stimulation or in the kidney cortex of db/db mice, and this was blocked by ki16425 treatment. LPA receptor 1 siRNA treatment inhibited LPA-induced TGFβ expression, whereas cells overexpressing LPA receptor 1 showed enhanced LPA-induced TGFβ expression. LPA treatment of SV40 MES13 cells increased phosphorylated glycogen synthase kinase (GSK)3β at Ser9 and induced translocation of sterol regulatory element-binding protein (SREBP)1 into the nucleus. Blocking GSK3β phosphorylation inhibited SREBP1 activation and consequently blocked LPA-induced TGFβ expression in SV40 MES13 cells. Phosphorylated GSK3β and nuclear SREBP1 accumulation were increased in the kidney cortex of db/db mice and ki16425 treatment blocked these pathways. Thus, LPA receptor 1 signaling increased TGFβ expression via GSK3β phosphorylation and SREBP1 activation, contributing to the development of diabetic nephropathy.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Li HY,Oh YS,Choi JW,Jung JY,Jun HSdoi
10.1016/j.kint.2016.11.010subject
Has Abstractpub_date
2017-06-01 00:00:00pages
1362-1373issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(16)30681-0journal_volume
91pub_type
杂志文章abstract：:In contrast to other nonsteroidal anti-inflammatory drugs (NSAIDs), sulindac has been reported to inhibit systemic prostaglandins (PGs) while not affecting renal PGs. We studied 11 normal volunteers who received placebo, ibuprofen, naproxen, or sulindac in a randomized, double-blind fashion. After control periods asse...
journal_title：Kidney international
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/ki.1985.11
更新日期：1985-01-01 00:00:00
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 ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2000.00051.x
更新日期：2000-05-01 00:00:00
abstract：:We demonstrate that salts of diatrizoate and iothalamate, radiographic contrast agents, depress the active transport of sodium in the urinary bladder of the Columbian toad, Bufo marinus. Isolated toad bladders were incubated in isotonic Ringer's solutions with isosmolar displacement of sodium chloride by contrast medi...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1975.11
更新日期：1975-02-01 00:00:00
abstract：BACKGROUND:High-efficiency hemodialysis may induce a deficiency in hydrosoluble vitamins. Supplementation with B-complex vitamins has been shown to lower serum homocysteine concentrations in several groups, but relatively few studies have concerned hemodialysis patients. Our objectives were to determine the status in B...
journal_title：Kidney international
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1523-1755.2000.00234.x
更新日期：2000-08-01 00:00:00
abstract：:A second generation hepatitis C virus recombinant immunoblot assay (RIBA) was used to screen stored perioperative serum from 641 renal allograft recipients. One hundred and nine (17%) were anti-HCV positive at the time of transplant. RIBA positivity was found to be an independent predictor of post-transplant liver dis...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1994.29
更新日期：1994-01-01 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：:Suzuki et al. analyzed a mouse model of erythropoietin-deficient anemia to show that during iron overload renal interstitial fibroblasts accumulate iron, and this impairs the hypoxia-driven transcription of the erythropoietin gene. The authors show that excess iron decreases levels of hypoxia-inducible transcription f...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1016/j.kint.2018.07.027
更新日期：2018-11-01 00:00:00
abstract：:Fibrates, the PPAR alpha ligand-like compounds increase the expression of proximal tubule liver fatty acid binding protein (L-FABP) and significantly decrease cisplatin-induced acute kidney injury. To study whether the bezafibrate-mediated upregulation of renal L-FABP was involved in this cytoprotective effect we trea...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2008.106
更新日期：2008-06-01 00:00:00
abstract：INTRODUCTION:Monocyte chemoattractant protein-1 (MCP-1) promotes renal inflammation, thereby contributing to acute and chronic nephropathies. Its production is stimulated by oxidative stress. Thus, this study tested whether pro-oxidant iron/carbohydrate complexes, used to treat iron deficiency, induce MCP-1 in renal/ex...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1111/j.1523-1755.2005.00565.x
更新日期：2005-10-01 00:00:00
abstract：:In this retrospective study, we analyzed clinical laboratory, and pathologic variables to determine their value in predicting survival and survival free of renal failure for 170 consecutive patients with idiopathic renal vasculitis and glomerulonephritis evaluated during a 15 year period. Of the 170 patients, 108 had ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1989.312
更新日期：1989-12-01 00:00:00
abstract：:The autoregulatory ability of the renal vascular system in the split hydronephrotic kidney was quantitated with intravital microscopy. The luminal diameters of the arcuate and interlobular arteries as well as the afferent and efferent arterioles were measured. Glomerular blood flow was determined by the dual slit tech...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1989.104
更新日期：1989-05-01 00:00:00
abstract：:Because the size of renal cysts in the native kidneys of patients with ADPKD who have been transplanted was found to be reduced when rapamycin was the immunosuppressant, we tested the involvement of the mTOR pathway in cyst enlargement. Here, male pcy mice, with mutation in one of the nephronophthisis genes, were trea...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2009.147
更新日期：2009-07-01 00:00:00
abstract：BACKGROUND:The clinical use of cyclosporine (CsA) is limited by its nephrotoxicity. Apoptosis, perhaps instigated by increased nitric oxide synthase (NOS) activity, may play a role in such toxicity. METHODS:Human mesangial cells, human tubular cells, human umbilical vein endothelial cells, or murine endothelial cells ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2000.00999.x
更新日期：2000-04-01 00:00:00
abstract：:Adynamic bone disease (ABD) is increasingly recognized, especially in dialysis patients treated with oral calcium carbonate, vitamin D supplements, or supraphysiological dialysate calcium. We undertook this study to assess the effect of lowering dialysate calcium on episodes of hypercalcemia, serum parathyroid hormone...
journal_title：Kidney international
pub_type： 杂志文章,随机对照试验
doi：10.1038/sj.ki.5001666
更新日期：2006-09-01 00:00:00
abstract：:Dual renin-angiotensin aldosterone (RAAS) blockade is associated with higher risk of hyperkalemia and has not been shown, in any outcome trial of validated renal end points, that is, doubling of creatinine, time to dialysis, or death, to be superior over other approaches. It shows promise in advanced proteinuric nephr...
journal_title：Kidney international
pub_type： 评论,杂志文章,评审
doi：10.1038/ki.2010.226
更新日期：2010-09-01 00:00:00
abstract：:Ambient glucose concentrations alter type 1 angiotensin II receptor (AT1R) expression in renal tissues. The direction of change in AT1R density may depend on the specific cell type and the capacity for that cell type to use glucose as an energy substrate. Given the effects of angiotensin II (Ang II) in proximal tubule...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1997.307
更新日期：1997-07-01 00:00:00
abstract：BACKGROUND:Autosomal-dominant medullary cystic kidney disease type 2 (MCKD2) is a tubulointerstitial nephropathy that causes renal salt wasting, hyperuricemia, gout, and end-stage renal failure in the fifth decade of life. The chromosomal locus for MCKD2 was localized on chromosome 16p12. Within this chromosomal region...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2003.00269.x
更新日期：2003-11-01 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：:To date direct evidence for the presence of a H-K-ATPase in the medulla comes from proton and potassium transport studies performed on K-restricted animals and K dependent ATP hydrolysis and Rb uptake in both normal and K-depleted animals. The present work examines K-dependent acidification in the medulla of rabbits o...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1992.392
更新日期：1992-11-01 00:00:00
abstract：:Exosomes are small membrane vesicles that are secreted from a variety of cell types into various body fluids including the blood and urine. These vesicles are thought to play a role in cell-cell interactions. CD24 is a small but extensively glycosylated protein linked to the cell surface by means of a glycosyl-phospha...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/sj.ki.5002486
更新日期：2007-11-01 00:00:00
abstract：:Thrombotic microangiopathy (TMA) is a poorly recognized cause of collapsing glomerulopathy. The frequency and significance of collapsing glomerulopathy associated with renal TMA have not been specifically studied in native kidney biopsy specimens. Here we retrospectively documented clinicopathologic features of 53 pat...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2016.07.021
更新日期：2016-12-01 00:00:00
abstract：:IgA nephropathy is the most common primary glomerulonephritis worldwide. Its frequent coexistence with inflammatory, infectious, or malignant processes raises the possibility of a pathologic rather than coincidental association. Major strides have been made to elucidate the underlying pathophysiologic events that culm...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1016/j.kint.2018.02.030
更新日期：2018-10-01 00:00:00
abstract：:The proportion of deceased donor kidneys procured for transplant but subsequently discarded has been growing steadily in the United States, but factors contributing to the rising discard rate remain unclear. To assess the reasons for and probability of organ discard we assembled a cohort of 212,305 deceased donor kidn...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2018.02.016
更新日期：2018-07-01 00:00:00
abstract：:The safety of dietary protein and phosphorous restriction was evaluated in the Modification of Diet in Renal Disease (MDRD) Study. In Study A, 585 patients with a glomerular filtration rate (GFR) of 25 to 55 ml/min/1.73 m2 were randomly assigned to a usual-protein diet (1.3 g/kg/day) or a low-protein diet (0.58 g/kg/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.1997.395
更新日期：1997-09-01 00:00:00
abstract：BACKGROUND:Hyperlipidemia is a risk factor for long-term renal transplant dysfunction, but no prospective clinical trials have investigated the effects of statin treatment on graft function in renal transplant recipients. The aim of the present study was to evaluate the effect of fluvastatin on long-term renal transpla...
journal_title：Kidney international
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1523-1755.2004.00919.x
更新日期：2004-10-01 00:00:00
abstract：:To determine the prognosis and risk factors for ischemic heart disease in chronic uremia, a cohort of 432 dialysis patients were followed prospectively from start of dialysis therapy until death or renal transplantation. Baseline demographic, clinical and echocardiographic data were obtained. After the initiation of d...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1996.201
更新日期：1996-05-01 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：BACKGROUND:We evaluated the effects of different concentrations of iron dextran administered through the intraperitoneal route, in iron-deficient rats, on hematocrit (Hct in percentage), serum iron (mg/dL), total iron binding capacity (TIBC in mg/dL), and the function and histology of the peritoneal membrane. METHODS:...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2001.059002764.x
更新日期：2001-02-01 00:00:00
abstract：BACKGROUND:Hypertension is a recognized complication of partial correction of anemia with recombinant human erythropoietin (epoetin) in hemodialysis patients. We used interdialytic ambulatory blood pressure (ABP) monitoring to study the effects of partially corrected anemia versus normal hematocrit (hct) on BP in hemod...
journal_title：Kidney international
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1523-1755.1999.00531.x
更新日期：1999-07-01 00:00:00
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
