Abstract:
:Stimulation of proximal tubule cell (PTC) growth in a variety of physiological and pathological renal conditions is preceded by increased renal production of transforming growth factor-beta 1 (TGF-beta 1) and by augmented tubular sodium transport via activated sodium hydrogen exchange (NHE). Since TGF-beta 1 has been shown to be an important paracrine and autocrine regulator of PTC growth, the hypothesis that TGF-beta 1 modulates basal and mitogen-stimulated PTC growth via an effect on NHE activity was examined. Confluent, quiescent, human PTC were incubated for 24 hours in serum-free media containing vehicle (control) or 1 ng/ml TGF-beta 1, in the presence or absence of 100 ng/ml insulin-like growth factor-1 (IGF-I). Under basal conditions, TGF-beta 1 inhibited thymidine incorporation (73.5 +/- 7.3% of control, P < 0.05), but exerted no effect on cellular protein content (97.4 +/- 10.7% of control), an index of hypertrophy. There was no significant alteration of NHE activity, measured as ethylisopropylamiloride (EIPA)-sensitive H+ efflux (2.72 +/- 0.50 vs. control 3.26 +/- 0.68 mmol/liter/min) or 22Na+ influx (2.20 +/- 0.23 vs. control 2.19 +/- 0.19 nmol/mg protein/min). When co-incubated with IGF-I. TGF-beta 1 induced significant PTC hypertrophy (116.9 +/- 8.2% of control, P < 0.05), which was not seen with either agent alone. TGF-beta 1 counteracted the stimulatory effect of IGF-I on DNA synthesis (TGF-beta 1 + IGF-I 103.0 +/- 7.3% vs. IGF-I alone 181.2 +/- 30.3% of control, P < 0.05), but did not affect IGF-I-stimulated EIPA-sensitive 22Na+ influx (3.63 +/- 0.63 vs. IGF-I alone 3.67 +/- 0.50 nmol/mg protein/min, P = NS, both vs. control 2.19 +/- 0.19 nmol/mg protein/min, P < 0.05). Similar results were obtained when NHE activity was measured as EIPA-sensitive H+ efflux. Moreover, the kinetics of NHE activation by the combination of TGF-beta 1 and IGF-I (involving an increase in Vmax) were identical to that previously found for PTC exposed to IGF-I alone. The study demonstrates that TGF-beta 1 elicits distinct PTC growth responses in the presence and absence of IGF-I, without modification of NHE activity. The combination of predominant PTC hypertrophy and enhanced proximal tubule Na+ reabsorption found in many conditions that are associated with renal growth is likely to require the integrated actions of both TGF-beta 1 and IGF-I.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Johnson DW,Saunders HJ,Brew BK,Poronnik P,Cook DI,Field MJ,Pollock CAdoi
10.1046/j.1523-1755.1998.00916.xsubject
Has Abstractpub_date
1998-06-01 00:00:00pages
1601-7issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(15)30579-2journal_volume
53pub_type
杂志文章abstract::We have developed an immunological procedure for measuring advanced glycosylation end-products (AGEs) in serum. Using this method, we measured AGEs in healthy volunteers, patients with diabetes, renal failure without treatment and in patients with renal failure, treated with hemodialysis (HD) or continuous ambulatory ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.262
更新日期:1994-07-01 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::Chronic inflammation is a complication of conventional hemodialysis that induces progressive cardiovascular damage. An apparently straightforward manipulation to treat this-removal of a large amount of uremic toxins by convection-has proven that the relationships between inflammation and convective techniques such as ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.81
更新日期:2014-08-01 00:00:00
abstract::Problems with vascular access are an important cause of morbidity and mortality in hemodialysis patients. We established a rodent model of arteriovenous fistula by anastomosing the end of a lateral vein to the side of the ventral artery of the rat tail. All operations were technically successful and in all animals the...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.207
更新日期:2008-08-01 00:00:00
abstract::Orskov and colleagues demonstrate the impact of birth weight on the mean age of end-stage renal disease (ESRD) in a large Danish ADPKD cohort. Each kilogram of birth weight extended the mean age of ESRD onset by 1.7 years. Placental insufficiency, activation of the renin-angiotensin-aldosterone system, increased fetal...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2012.8
更新日期:2012-05-01 00:00:00
abstract::From the urine of patients with calcium nephrolithiasis, and of control subjects, we isolated organic substances according to molecular size and tested them for effects on calcium oxalate precipitation. Nine subgroup materials of varying sizes were prepared by ultrafiltration and Sephadex G-200 column chromatography f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.33
更新日期:1982-02-01 00:00:00
abstract::Recent studies including the current article by Sawinski et al. demonstrate that hepatitis C virus (HCV) infection is associated with worse outcomes in kidney transplant recipients with and without HIV infection. We comment on the significance of these findings in the context of newer options for the treatment of HCV ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2015.180
更新日期:2015-08-01 00:00:00
abstract:UNLABELLED:The paracellular permeability of opossum kidney cells, a proximal tubule cell line. BACKGROUND:The regulation of the unusually leaky paracellular pathway of the proximal tubule is poorly understood partially because of the lack of an appropriate in vitro cell model. In this study, we determined whether the ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00787.x
更新日期:1999-12-01 00:00:00
abstract::Alterations in red blood cell sodium (Na) transport have been described in chronic renal failure. This study examines the possible impact of uremia on two ouabain-insensitive pathways, the Na/H antiporter and the Cl-/NaCO3- anion exchanger. The Vmax of Na/H antiporter measured as Na influx driven by outward H gradient...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.283
更新日期:1993-09-01 00:00:00
abstract::Prostaglandin E2 (PGE2) may be an important negative feedback modulator of endothelin-1 (ET-1)-stimulated mesangial cell proliferation and contraction. Recent studies suggest that ET-1 may induce prolonged mesangial cell PGE2 production, however the mechanism of this effect is unknown. The current study was undertaken...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.6
更新日期:1995-01-01 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::We compared the effects of calcitriol and doxercalciferol, in combination with either calcium carbonate or sevelamer, on bone, mineral, and fibroblast growth factor-23 (FGF-23) metabolism in patients with secondary hyperparathyroidism. A total of 60 pediatric patients treated with peritoneal dialysis were randomized t...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2010.352
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:In X-linked Alport syndrome, mutations in the COL4A5 gene encoding the alpha 5 chain of type IV collagen result in progressive renal failure. This nephropathy appears to relate to the arrest of a switch from an alpha 1/alpha 2 to an alpha 3/alpha 4/alpha 5 network of type IV collagen in the developing glomer...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00188.x
更新日期:1998-12-01 00:00:00
abstract::Renin secretion was compared in vivo and in vitro among five groups of rats, each group subjected to a different sodium balance for 10 to 14 days. The state of the renin-angiotensin system in vivo was evaluated by measuring the renal renin (RR) and the plasma renin concentration (PRC) in both anesthetized and nonanest...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.71
更新日期:1980-05-01 00:00:00
abstract:BACKGROUND:The interaction between tubular epithelial cells and calcium oxalate crystals or oxalate ions is a very precarious event in the lithogenesis. Urine contains ions, glycoproteins and glycosaminoglycans that inhibit the crystallization process and may protect the kidney against lithogenesis. We examined the eff...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00577.x
更新日期:2005-10-01 00:00:00
abstract::An expression profile is a list based on a large scale sequencing of 1000 cDNA clones, showing the expressed genes and the abundance of their transcripts in a given cell or tissue (Okubo K et al: Nature Genet 2:173, 1992). We constructed an expression profile of mouse renal proximal tubules (PT) carefully isolated by ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00808.x
更新日期:1998-03-01 00:00:00
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 ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.39
更新日期:2011-06-01 00:00:00
abstract::Continuous antigen stimulation during chronic infection or malignancy can promote functional T cell silencing, a phenomenon called T cell exhaustion. The prevalence and impact of T cell exhaustion following organ transplantation, another immune stimulus with persistently high antigen load, are unknown. Here, we charac...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.01.040
更新日期:2019-08-01 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::Previously, uremic toxins were sometimes regarded as a large, mysterious, but also anonymous group of factors potentially contributing to morbidity and mortality in end-stage renal disease. By identifying the protein-bound solute p-cresol as a risk factor for mortality in dialysis patients, Bammens and colleagues for ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5000236
更新日期:2006-03-01 00:00:00
abstract:BACKGROUND:Erythropoietin is known to improve outcomes in patients with anemia from chronic renal disease. However, there is uncertainty about the optimal timing of initiation of erythropoietin treatment in predialysis patients with non-severe anemia. METHODS:We conducted a randomized controlled trial of early versus ...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2004.00797.x
更新日期:2004-08-01 00:00:00
abstract::We have recently presented evidence that endogenous nitric oxide (NO) and prostaglandins (PGs) modulate angiotensin II (Ang II) action in microperfused afferent arterioles (Af-Arts). Because flow may be a physiological stimulus of endothelial release of NO and PGs, we tested the hypothesis that flow through the lumen ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.55
更新日期:1996-02-01 00:00:00
abstract:BACKGROUND:The aim of this study was to define cut-off values for serum creatinine as an indicator of several levels of renal impairment. METHODS:To identify the suitable values, receiver operating characteristic curves were constructed based on the data of 984 laboratory assessments of renal function. The glomerular ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00411.x
更新日期:1999-05-01 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:Unilateral ureteral obstruction (UUO) leads to interstitial fibrosis of the obstructed kidney, and TGF-beta is considered to play an important role in this fibrotic process. Smad7 has been recently identified as an antagonist of TGF-beta signaling. To investigate whether this novel molecule can be exploited ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.0610s1094.x
更新日期:2002-01-01 00:00:00
abstract::Levels of prepro epidermal growth factor (EGF) mRNA in renal cortical tissue and urinary EGF excretion have been determined during cisplatin and ischemia-induced acute renal failure in the rat. Northern analysis of polyadenylated RNAs of kidney cortical tissue showed diminished renal preproEGF mRNA in rats injected wi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.266
更新日期:1989-11-01 00:00:00
abstract:BACKGROUND:Increasing proteinuria in kidney disease is associated with an increased risk of renal failure. Urinary proteins such as albumin induce inflammatory signaling and gene expression in tubular epithelial cells (TECs). Fibronectin is an extracellular matrix protein that can exist in soluble form and is excreted ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00667.x
更新日期:2005-11-01 00:00:00
abstract::The development of effective therapies for acute kidney injury (AKI) has been hindered by delayed diagnosis in the clinical setting, varying definitions of AKI, and limited prognostic information. In a study by Portilla et al., elevations in liver fatty acid-binding protein (L-FABP) were found to predict AKI in childr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002739
更新日期:2008-02-01 00:00:00
abstract::While hemodialysis therapy in its present form is capable of sustaining life, dialysis patients are not metabolically normal and we are unable to say what technical factors contribute adequate therapy. Recent efforts to resolve these problems have led to the assumption that substances in the molecular weight range of ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1976.126
更新日期:1976-11-01 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