Histone deacetylase inhibition attenuates diabetes-associated kidney growth: potential role for epigenetic modification of the epidermal growth factor receptor.


: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.


Kidney Int


Kidney international


Gilbert RE,Huang Q,Thai K,Advani SL,Lee K,Yuen DA,Connelly KA,Advani A




Has Abstract


2011-06-01 00:00:00














  • Modulation of salt transport rate affects DNA synthesis in vivo in rat renal tubules.

    abstract::In adult male Wistar rats we investigated whether cell proliferation contributes to salt load-induced hypertrophy of distal tubules. In one treatment group salt transport in the thick ascending limb (TAL) was inhibited by furosemide (7.5 mg/100 g body wt/24 hr, via osmotic minipump) and stimulated in the successive di...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Loffing J,Le Hir M,Kaissling B

    更新日期:1995-06-01 00:00:00

  • Primary outcomes of the Monitoring in Dialysis Study indicate that clinically significant arrhythmias are common in hemodialysis patients and related to dialytic cycle.

    abstract::Sudden death is one of the more frequent causes of death for hemodialysis patients, but the underlying mechanisms, contribution of arrhythmia, and associations with serum chemistries or the dialysis procedure are incompletely understood. To study this, implantable loop recorders were utilized for continuous cardiac rh...

    journal_title:Kidney international

    pub_type: 杂志文章,多中心研究


    authors: Roy-Chaudhury P,Tumlin JA,Koplan BA,Costea AI,Kher V,Williamson D,Pokhariyal S,Charytan DM,MiD investigators and committees.

    更新日期:2018-04-01 00:00:00

  • Lipid abnormalities associated with urinary albumin excretion rate in Taiwanese type 2 diabetic patients.

    abstract:BACKGROUND:The purpose of this study was to examine the lipid abnormalities associated with urinary albumin excretion rate (UAER) in type 2 diabetic patients. METHODS:A total of 275 (122 men and 153 women; aged 60.6 +/- 11.1 years) patients were selected with stringent criteria to prevent confounders. Normoalbuminuria...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Tseng CH

    更新日期:2005-04-01 00:00:00

  • Triptolide reduces proteinuria in experimental membranous nephropathy and protects against C5b-9-induced podocyte injury in vitro.

    abstract::Membranous nephropathy is a major cause of nephrotic syndrome in adults where podocyte injuries were found to mediate the development of proteinuria. Triptolide, a major active component of Tripterygium wilfordii Hook F, has potent immunosuppressive, anti-inflammatory and antiproteinuric effects. To study its antiprot...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Chen ZH,Qin WS,Zeng CH,Zheng CX,Hong YM,Lu YZ,Li LS,Liu ZH

    更新日期:2010-06-01 00:00:00

  • Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. Durham Renal Osteodystrophy Study Group.

    abstract:UNLABELLED:Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. BACKGROUND:In the management of patients with mild secondary hyperparathyroidism, it is not known whether calcium supplementation alone is sufficient to correct abnormalities in bone and mineral metabolism or if calcit...

    journal_title:Kidney international

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Indridason OS,Quarles LD

    更新日期:2000-01-01 00:00:00

  • Practical management of C3 glomerulopathy and Ig-mediated MPGN: facts and uncertainties.

    abstract::In recent years, a substantial body of experimental and clinical work has been devoted to C3 glomerulopathy and Ig-mediated membranoproliferative glomerulonephritis. Despite the rapid accumulation of data, several uncertainties about these 2 rare forms of nephropathies persist. They concern their pathophysiology, clas...

    journal_title:Kidney international

    pub_type: 杂志文章,评审


    authors: Fakhouri F,Le Quintrec M,Frémeaux-Bacchi V

    更新日期:2020-11-01 00:00:00

  • Diagnosis of renovascular disease by intra- and extrarenal Doppler scanning.

    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


    authors: Krumme B,Blum U,Schwertfeger E,Flügel P,Höllstin F,Schollmeyer P,Rump LC

    更新日期:1996-10-01 00:00:00

  • Modulation of Ca2+-activated K+ channel in renal artery endothelium in situ by nitric oxide and reactive oxygen species.

    abstract:BACKGROUND:Endothelium-derived nitric oxide and reactive oxygen species (ROS) have been proposed to regulate vascular tone by complex mechanisms, including the modulation of ion channel function. In endothelial function itself, activation of Ca2+-activated K+ channels (KCa) plays a crucial role by inducing hyperpolariz...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Brakemeier S,Eichler I,Knorr A,Fassheber T,Köhler R,Hoyer J

    更新日期:2003-07-01 00:00:00

  • Differential contribution of C5aR and C5b-9 pathways to renal thrombic microangiopathy and macrovascular thrombosis in mice carrying an atypical hemolytic syndrome-related factor H mutation.

    abstract::Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) caused by dysregulated complement activation. Clinically, aHUS is effectively treated by an anti-C5 monoclonal antibody (mAb) but whether the disease is mediated by the C5a receptor (C5aR) or C5b-9 pathway, or both, is unknown. Her...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Ueda Y,Miwa T,Ito D,Kim H,Sato S,Gullipalli D,Zhou L,Golla M,Song D,Dunaief JL,Palmer MB,Song WC

    更新日期:2019-07-01 00:00:00

  • Therapy of relapsing minimal-change disease in adults: a new approach?

    abstract::Multiple-relapsing minimal-change disease (MCD) often requires exposure to potentially toxic agents in an attempt to achieve a lasting remission of nephrotic syndrome. Munyentwali and co-workers describe an experience using rituximab in adults with multiple-relapsing MCD that supports both efficacy and safety of this ...

    journal_title:Kidney international

    pub_type: 评论,杂志文章


    authors: Glassock RJ

    更新日期:2013-03-01 00:00:00

  • Nutrition in end-stage renal disease.

    abstract::In summary, it is evident that malnutrition is highly prevalent in ESRD patients. This is clearly related to multiple factors encountered during the pre-dialysis stage, as well as during maintenance dialysis therapy. A body of evidence highlights the existence of relationship between malnutrition and outcome in this p...

    journal_title:Kidney international

    pub_type: 杂志文章,评审


    authors: Ikizler TA,Hakim RM

    更新日期:1996-08-01 00:00:00

  • Regulatory interactions of alphabeta and gammadelta T cells in glomerulonephritis.

    abstract:BACKGROUND:Several lines of evidence suggest that cellular immune mechanisms contribute to glomerulonephritis. METHODS:The roles of alphabeta and gammadelta T cells in the pathogenesis of glomerulonephritis were investigated in a model of nephrotoxic nephritis in mice deficient in either T-cell population [T-cell rece...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Rosenkranz AR,Knight S,Sethi S,Alexander SI,Cotran RS,Mayadas TN

    更新日期:2000-09-01 00:00:00

  • Nephrin mediates actin reorganization via phosphoinositide 3-kinase in podocytes.

    abstract::Nephrin is a slit diaphragm protein critical for structural and functional integrity of visceral glomerular epithelial cells (podocytes) and is known to be tyrosine phosphorylated by Src family kinases. We studied the role of phosphoinositide 3-kinase (PI3K), activated via the phosphorylation of nephrin, in actin cyto...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Zhu J,Sun N,Aoudjit L,Li H,Kawachi H,Lemay S,Takano T

    更新日期:2008-03-01 00:00:00

  • Lysyl oxidase like-2 contributes to renal fibrosis in Col4α3/Alport mice.

    abstract::Lysyl oxidase like-2 (LOXL2) is an amine oxidase with both intracellular and extracellular functions. Extracellularly, LOXL2 promotes collagen and elastin crosslinking, whereas intracellularly, LOXL2 has been reported to modify histone H3, stabilize SNAIL, and reduce cell polarity. Although LOXL2 promotes liver and lu...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Cosgrove D,Dufek B,Meehan DT,Delimont D,Hartnett M,Samuelson G,Gratton MA,Phillips G,MacKenna DA,Bain G

    更新日期:2018-08-01 00:00:00

  • Lipopolysaccharide-induced MCP-1 gene expression in rat tubular epithelial cells is nuclear factor-kappaB dependent.

    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


    authors: Wang Y,Rangan GK,Goodwin B,Tay YC,Harris DC

    更新日期:2000-05-01 00:00:00

  • Deletion of scavenger receptor A protects mice from progressive nephropathy independent of lipid control during diet-induced hyperlipidemia.

    abstract::Scavenger receptor A (SR-A) is a key transmembrane receptor in the endocytosis of lipids and contributes to the pathogenesis of atherosclerosis. To assess its role in hyperlipidemic chronic kidney disease, wild-type and SR-A-deficient (knockout) mice underwent uninephrectomy followed by either normal or high-fat diet....

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Wang W,He B,Shi W,Liang X,Ma J,Shan Z,Hu Z,Danesh FR

    更新日期:2012-05-01 00:00:00

  • Toxic acute tubular necrosis following treatment with zoledronate (Zometa).

    abstract:BACKGROUND:Renal failure and toxic acute tubular necrosis (ATN) may be seen following exposure to a variety of therapeutic agents. Zoledronate (Zometa) is a new, highly potent bisphosphonate used in the treatment of hypercalcemia of malignancy. We report the first clinical-pathologic study of nephrotoxicity associated ...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Markowitz GS,Fine PL,Stack JI,Kunis CL,Radhakrishnan J,Palecki W,Park J,Nasr SH,Hoh S,Siegel DS,D'Agati VD

    更新日期:2003-07-01 00:00:00

  • The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy.

    abstract::A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persi...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Fernández-Juárez G,Rojas-Rivera J,Logt AV,Justino J,Sevillano A,Caravaca-Fontán F,Ávila A,Rabasco C,Cabello V,Varela A,Díez M,Martín-Reyes G,Diezhandino MG,Quintana LF,Agraz I,Gómez-Martino JR,Cao M,Rodríguez-Moreno A,

    更新日期:2020-11-07 00:00:00

  • Tumor necrosis factor-alpha and lipopolysaccharide induce apoptotic cell death in bovine glomerular endothelial cells.

    abstract:BACKGROUND:The glomerular endothelial cell is a specialized microvascular cell type involved in the regulation of glomerular ultrafiltration. During gram-negative sepsis, glomerulonephritis, and acute renal failure, bacterial lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) may cause severe cell dam...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Messmer UK,Briner VA,Pfeilschifter J

    更新日期:1999-06-01 00:00:00

  • Impact of uremia on female reproductive cyclicity, ovulation, and luteinizing hormone in the rat.

    abstract:BACKGROUND:Impaired reproductive function accompanies chronic renal insufficiency (uremia) in both the human and experimental animal. Clinical hypogonadism occurs in both genders. The present studies were designed to investigate possible anti-ovulatory effects of uremia in the female rat, a species that produces multip...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Krieg RJ,Tokieda K,Chan JC,Veldhuis JD

    更新日期:2000-08-01 00:00:00

  • Morphometric study of glomerular slit diaphragms fixed by rapid-freezing and freeze-substitution.

    abstract::The widths of slit diaphragms in rat glomeruli were quantitatively measured on electron micrographs obtained by the rapid-freezing and freeze-substitution (FS) fixation method and compared to those prepared by conventional chemical fixation procedures, such as tannic acid, glutaraldehyde and osmium tetroxide (TGO) or ...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Furukawa T,Ohno S,Oguchi H,Hora K,Tokunaga S,Furuta S

    更新日期:1991-10-01 00:00:00

  • Electrophysiological indices of CNS function in hemodialysis and CAPD.

    abstract::Fourteen Center hemodialysis (CHD) patients, 13 continuous ambulatory peritoneal dialysis (CAPD) patients, and 10 normals matched by group for age and sex were compared using a battery of evoked (EP) and event-related (ERP) brain potential measures to determine the effects on central nervous system (CNS) functioning o...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Marsh JT,Brown WS,Wolcott D,Landsverk J,Nissenson AR

    更新日期:1986-12-01 00:00:00

  • Glucocorticoid receptors, in vitro steroid sensitivity, and cytokine secretion in idiopathic nephrotic syndrome.

    abstract:BACKGROUND:Glucocorticoids (GC) represent the mainstay of treatment of idiopathic nephrotic syndrome (INS) and might be involved in the pathogenesis of the disease. We evaluated basal secretion of cortisol, number and affinity of glucocorticoid receptors, dexamethasone (Dex)-mediated inhibition of concanavalin-A (Con-A...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Carlotti AP,Franco PB,Elias LL,Facincani I,Costa EL,Foss N,Moreira AC,de Castro M

    更新日期:2004-02-01 00:00:00

  • High glomerular permeability of bikunin despite similarity in charge and hydrodynamic size to serum albumin.

    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


    authors: Lindström KE,Blom A,Johnsson E,Haraldsson B,Fries E

    更新日期:1997-04-01 00:00:00

  • Transcription factor FoxO1, the dominant mediator of muscle wasting in chronic kidney disease, is inhibited by microRNA-486.

    abstract::Chronic kidney disease (CKD) accelerates muscle protein degradation by stimulating the ubiquitin proteasome system through activation of the E3 ligases, Atrogin-1/MAFbx and MuRF-1. Forkhead transcription factors (FoxOs) can control the expression of these E3 ligases, but the contribution of individual FoxOs to muscle ...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Xu J,Li R,Workeneh B,Dong Y,Wang X,Hu Z

    更新日期:2012-08-01 00:00:00

  • Urinary matrix calculi consisting of microfibrillar protein in patients on maintenance hemodialysis.

    abstract::In seven patients on maintenance hemodialysis, de novo recurrent renal stone formation was observed. In all patients, the underlying disease was glomerulonephritis, with or without the nephrotic syndrome. All patients had considerable persistent proteinuria. The stones consisted predominantly of protein, as revealed b...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Bommer J,Ritz E,Tschöpe W,Waldherr R,Gebhardt M

    更新日期:1979-12-01 00:00:00

  • Kidney-specific reconstitution of the A1 adenosine receptor in A1 adenosine receptor knockout mice reduces renal ischemia-reperfusion injury.

    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


    authors: Kim M,Chen SW,Park SW,Kim M,D'Agati VD,Yang J,Lee HT

    更新日期:2009-04-01 00:00:00

  • Antigen presentation by dendritic cells in renal lymph nodes is linked to systemic and local injury to the kidney.

    abstract:BACKGROUND:Dendritic cells (DCs) uniquely serve as conduits between innate and cognate arms of the immune system. The normal kidney contains an extensive population of interstitial DCs but their role in the pathogenesis of acute renal injury is not known. METHODS:Renal DCs were studied by flow cytometric analysis of c...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Dong X,Swaminathan S,Bachman LA,Croatt AJ,Nath KA,Griffin MD

    更新日期:2005-09-01 00:00:00

  • Influence of systemically applied angiotensin II on the microcirculation of glomerular capillaries in the rat.

    abstract::The effect of intravenous infusion of angiotensin II on microvascular parameters of the renal microcirculation of rats was studied. With the aid of fluorescence microscopy and a high sensitivity video system we observed the passage of fluorescence-labeled erythrocytes through single glomerular capillaries on the surfa...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Zimmerhackl B,Parekh N,Kücherer H,Steinhausen M

    更新日期:1985-01-01 00:00:00

  • The calcium sensing receptor modulates fluid reabsorption and acid secretion in the proximal tubule.

    abstract::The proximal tubule uses a complex process of apical acid secretion and basolateral bicarbonate absorption to regulate both luminal acidification and fluid absorption. One of the primary regulators of apical acid secretion is the luminal sodium-hydrogen exchanger expressed along the apical membrane of the proximal tub...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Capasso G,Geibel PJ,Damiano S,Jaeger P,Richards WG,Geibel JP

    更新日期:2013-08-01 00:00:00