Abstract:
:Clinical trials and experimental studies have highlighted the importance of epigenetic processes in the development of diabetic complications. One of the earliest features of diabetic nephropathy is renal enlargement. The epidermal growth factor (EGF) has a pivotal role in the development of diabetic nephromegaly and transactivation of its receptor has been implicated in the pathogenesis of later-stage disease. As EGF signaling is altered by the acetylation status of histone proteins, we measured the effects of the histone deacetylase (HDAC) inhibitor, vorinostat, in mediating renal enlargement in diabetes focusing on the EGF-EGF receptor (EGFR) axis. In cultured proximal tubule (normal rat kidney) cells, vorinostat treatment reduced EGFR protein and mRNA, and attenuated cellular proliferation. Within 72 h of diabetes induction with streptozotocin, urinary EGF excretion was increased approximately threefold and was unaffected by vorinostat, even though the kidneys of vorinostat-treated diabetic rats had reduced tubular epithelial cell proliferation. Daily treatment of diabetic rats with vorinostat for 4 weeks blunted renal growth and glomerular hypertrophy. Thus, early renal changes in diabetes are amenable to epigenetic intervention. Attenuating effects of HDAC inhibition, although multifactorial, are likely to be mediated in part through downregulation of the EGFR.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Gilbert RE,Huang Q,Thai K,Advani SL,Lee K,Yuen DA,Connelly KA,Advani Adoi
10.1038/ki.2011.39subject
Has Abstractpub_date
2011-06-01 00:00:00pages
1312-21issue
12eissn
0085-2538issn
1523-1755pii
S0085-2538(15)54746-7journal_volume
79pub_type
杂志文章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 relationship between blood pressure (BP) and mortality in hemodialysis patients has remained controversial. Some studies suggested that a lower pre- or postdialysis BP was associated with excess mortality, while others showed poorer outcome in patients with uncontrolled hypertension. We conducted a multi...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1523-1755.2004.00812.x
更新日期:2004-09-01 00:00:00
abstract::Whole-genome microarrays identify large numbers of gene expression changes that appear specifically related to disease states such as antineutrophil cytoplasmic autoantibody (ANCA) and systemic lupus erythematosus. Although understanding this enormous volume of esoteric data is difficult, a few basic concepts regardin...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002492
更新日期:2007-10-01 00:00:00
abstract::Class II gene products of the major histocompatibility complex (MHC) are not expressed usually in abundance on normal epithelium. The cell surface visibility of such proteins for the immune system is thought to be limited protectively in order to minimize inflammation consequent to the recognition of self-antigens in ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.191
更新日期:1991-07-01 00:00:00
abstract::The thick ascending limb of Henle's loop ( TAL ) develops a specific and consistent structural lesion during perfusion of the isolated rat kidney that progresses from mitochondrial swelling at 15 min to complete cellular disruption at 90 min. Because it seemed possible that damage localized to this metabolically activ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.9
更新日期:1984-01-01 00:00:00
abstract::Tissandié and colleagues report in this issue on their studies of IgA1 glycosylation and biological activities of IgA1-containing circulating immune complexes in patients with alcoholic cirrhosis who developed secondary renal disease with IgA deposits, secondary IgA nephropathy. Their seminal findings demonstrate abno...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2011.302
更新日期:2011-12-01 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::Chronic kidney disease (CKD) remains one of the leading causes of death in the developed world, and acute kidney injury (AKI) is now recognized as a major risk factor in its development. Understanding the factors leading to CKD after acute injury are limited by current animal models of AKI, which concurrently target v...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.20
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND:Autosomal-dominant medullary cystic kidney disease (ADMCKD), a hereditary chronic interstitial nephropathy, recently attracted attention because of the cloning or mapping of certain gene loci, namely NPHP1, NPHP2 and NPHP3 for familial juvenile nephronophthisis (NPH) and MCKD1 and MCKD2 for the adult form of...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2002.kid581.x
更新日期:2002-10-01 00:00:00
abstract:BACKGROUND:In a prior study the 21-aminosteroid (lazaroid) U74389F provided in vivo protection from oxidative stress when used as a preventive therapy in ischemia-reperfusion injury in the kidney. As the cell membrane is the principal site for lipoperoxidation, in the current study the very lipophilic 2-methylaminochro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00072.x
更新日期:1998-09-01 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:UNLABELLED:Hereditary systemic amyloidosis associated with a new apolipoprotein AII stop codon mutation Stop78Arg. BACKGROUND:Mutations in the gene for apolipoprotein AII (apoAII) have recently been found to cause hereditary renal amyloidosis. In each case amyloid deposition has been associated with a peptide extensio...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00047.x
更新日期:2003-07-01 00:00:00
abstract:BACKGROUND:Although renal protective effect of interrupting the inflammatory process is well established, it is still controversial if it also prevents the glomerular hemodynamic disturbances that initiate renal injury. We investigated the effects of suppressing inflammation with mycophenolate mofetil (MMF) on glomerul...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00811.x
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND:The clinical demographics of chronic dialysis patients are changing worldwide. However, long-term data from regional dialysis registries have not yet been analyzed and reported. METHODS:The Okinawa Dialysis Study (OKIDS) registry included all chronic dialysis patients treated in Okinawa, Japan, since 1971. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00147.x
更新日期:2002-02-01 00:00:00
abstract::Diabetic nephropathy shows a higher incidence in male subjects, which may in part be owing to genetic factors. The angiotensin II type 2 receptor (AT2), present in the renal glomerulus, may oppose the deleterious effects of the type I receptor (AT1) through vasodilatation and growth inhibition. We determined whether t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000348
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:Genetic polymorphisms of the angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) genes are associated with increased risk of hypertension and left ventricular hypertrophy (LVH) in hypertensive subjects. However, the extent to which these polymorphisms are related to LVH and remodeling in dialysis p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00933.x
更新日期:2003-05-01 00:00:00
abstract::Clinical and experimental studies have shown that serum aluminum (Al) is bound to transferrin and that cellular uptake of Al appears to be mediated by transferrin receptors. Based on these findings it is widely believed that intestinal Al absorption occurs via iron-specific, transferrin-dependent pathways and that iro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.509
更新日期:1996-12-01 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:The link between dialysis "vintage" (length of time on dialysis in months to years) and survival has been difficult to define, largely because of selection effects. End-stage renal disease (ESRD) is thought to be a wasting illness, but there are no published reports describing the associations between vintag...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00945.x
更新日期:2000-03-01 00:00:00
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: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:Wegener's granulomatosis (WG) is characterized by systemic vasculitis with crescentic glomerulonephritis (CGN) and circulating autoantibodies directed against neutrophil cytoplasmic antigens (ANCA). Proteinase 3 (PR-3), a neutral serine proteinase in neutrophils implicated in the growth control of myeloid ce...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00100.x
更新日期:2000-06-01 00:00:00
abstract::This study evaluated risk factors for end-stage renal disease (ESRD) and the prognostic significance of serum creatinine levels in a community-based mass screening. We used the registries of both community-based mass screening and chronic dialysis programs. In 1983, a total of 107,192 subjects over 18 years of age (51...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.119
更新日期:1997-03-01 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::Lipid abnormalities have been suggested as a major cause of the accelerated atherosclerosis and the high incidence of coronary heart disease in chronic renal failure patients. In the present work the postprandial lipoprotein metabolism was studied in chronic dialysis patients with or without fasting hypertriglyceridem...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.411
更新日期:1992-11-01 00:00:00
abstract::Angiotensin converting enzyme (ACE) inhibitors are known to lower urinary protein excretion in human renal disease. This proteinuria lowering effect of ACE inhibition has been hypothesized to be a result of renal hemodynamic changes due to the inhibition of angiotensin II (Ang II) production. To test this hypothesis w...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1991.268
更新日期:1991-10-01 00:00:00
abstract:BACKGROUND:The feasibility of simultaneously infusing glucose and amino acid (AA)-based peritoneal dialysis solutions was tested to determine whether peritoneal dialysis patients could achieve an adequate nonprotein calorie/nitrogen ratio while preventing a marked increase in blood urea nitrogen (BUN), which is usually...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590051967.x
更新日期:2001-05-01 00:00:00
abstract::The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) is thought to be a protective enzyme of the mineralocorticoid receptor (MR). We have previously demonstrated (Bonvalet et al, J Clin Invest 86:832-837, 1990) that 11 beta-OHSD is colocalized with MR along the rabbit nephron. In the present study, we examin...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.260
更新日期:1992-07-01 00:00:00
abstract:BACKGROUND:Atherosclerotic vascular disease is the leading cause of death in patients with diabetes mellitus and end-stage renal disease. Advanced glycation end products (AGEs) are strongly suggested to be involved in the pathogenesis of atherosclerosis in these patients who also frequently experience infectious compli...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00157.x
更新日期:1998-11-01 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