Abstract:
BACKGROUND:Although apoptosis has been linked to the renal cell deletion and ensuing renal fibrosis, its regulating mechanisms remain obscure. Of the known regulators of apoptosis, the best characterized is the Bax to Bcl-2 ratio. However, its importance in controlling apoptosis in glomerulonephritis is unclear. Here, using the nephrotoxic nephritis (NTN) model, we evaluated Bax/Bcl-2 in relation to changes in the apoptosis co-ordination enzyme, caspase-3. METHODS:Kidneys were harvested at days 7, 15, 30 and 45 post-injection of anti-glomerular basement membrane antibody into Wistar Kyoto rats. These were analyzed for apoptosis (in situ end labeling of fragmented DNA, light and electron microscopy), Bax/Bcl-2 protein (Western blotting), mRNA (Northern blotting) and distribution (immunohistochemistry), as well as caspase-3 activity (substrate cleavage assay), inflammation (ED1 staining), proliferation (proliferating cell nuclear antigen staining) and fibrosis (Masson's Trichrome staining). RESULTS:Bax mRNA was significantly increased while that of Bcl-2 was decreased throughout the time course (+265% and -62% by day 45). Increased Bax and decreased Bcl-2 protein were noted, significantly so on day 7 (+177% and -21%) and day 45 (+363% and -17%). Bax protein was observed in dilated and atrophic tubules, sclerotic glomeruli and inflamed interstitium, while Bcl-2 was only visible in atrophic tubules. The ratios of Bax to Bcl-2 mRNA and protein were significantly increased at all time points. These correlated (P < 0.05) with up-regulated caspase-3 activity (r = 0.742 and 0.531), apoptosis (r = 0.712 and 0.540), proliferation (r = 0.611, mRNA only), inflammation (ED1+, r = 0.474 and 0.419) and fibrosis (r = 0.474 and 0.729). CONCLUSIONS:Our findings suggest that the changes in the ratio of Bax to Bcl-2 may contribute to the caspase-3 activation and the modulation of renal apoptosis associated with renal inflammation, tubular atrophy and renal fibrosis in experimental glomerulonephritis.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Yang B,Johnson TS,Thomas GL,Watson PF,Wagner B,Furness PN,El Nahas AMdoi
10.1111/j.1523-1755.2002.kid587.xsubject
Has Abstractpub_date
2002-10-01 00:00:00pages
1301-13issue
4eissn
0085-2538issn
1523-1755pii
S0085-2538(15)48672-7journal_volume
62pub_type
杂志文章abstract::Progressive kidney fibrosis precedes end-stage renal failure in up to a third of patients with diabetes mellitus. Elevated intra-renal transforming growth factor-beta (TGF-beta) is thought to underlie disease progression by promoting deposition of extracellular matrix and epithelial-mesenchymal transition. GW788388 is...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002717
更新日期:2008-03-01 00:00:00
abstract::Chronic cyclosporine (CsA) nephrotoxicity is a major complication of heart, bone marrow, and renal transplantation, and is characterized in humans by striped interstitial fibrosis, tubular dilatation and atrophy, and hyalinization of hilar arterioles. This last feature is highly specific for cyclosporine injury and ha...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.311
更新日期:1995-08-01 00:00:00
abstract::Accumulation of extracellular matrix within the mesangium is an important event in the development of glomerular disease. In this report we have used indirect immunofluorescence to positively identify a number of constituents of the mesangial matrix synthesized by rat mesangial cells (RMC) in vitro including laminin, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.412
更新日期:1995-10-01 00:00:00
abstract::The cellular redox state is altered in a number of pathological conditions, including various forms of glomerular injury and diabetes. For example, glucose, via the pentose phosphate pathway generates NADPH, which maintains glutathione (GSH) (part of a major intracellular reducing system) in its reduced state. GSH in ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.286
更新日期:1994-08-01 00:00:00
abstract:BACKGROUND:Hyperhomocysteinemia is a risk factor for atherosclerosis that is common in chronic renal failure (CRF), but its cause is unknown. Homocysteine metabolism is linked to betaine-homocysteine methyl transferase (BHMT), a zinc metalloenzyme that converts glycine betaine (GB) to N,N dimethylglycine (DMG). DMG is ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00743.x
更新日期:2001-06-01 00:00:00
abstract::Autosomal dominant polycystic kidney disease (ADPKD) is associated with a urine-concentrating defect attributed to renal cystic changes. As PKD genes are expressed in the brain, altered central release of arginine vasopressin could also play a role. In order to help determine this we measured central and nephrogenic c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.225
更新日期:2012-11-01 00:00:00
abstract::The cannabinoid receptor type 2 (CB2) is a G protein-coupled seven transmembrane receptor that transmits endogenous cannabinoid signaling. The role of CB2 in the pathogenesis of kidney injury and fibrosis remains poorly understood. Here we demonstrate that CB2 was induced, predominantly in kidney tubular epithelium, i...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.05.023
更新日期:2018-10-01 00:00:00
abstract::The hypoxia-inducible factor-1 (HIF-1) was first described as a DNA binding activity that specifically recognizes an 8 bp hypoxia response element (HRE) known to be essential for oxygen-regulated erythropoietin gene expression. In electrophoretic mobility shift assays (EMSAs) HIF-1 DNA binding activity is only detecta...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.80
更新日期:1997-02-01 00:00:00
abstract::The prevalence of raised Na+/Li+ countertransport (CT) activity (greater than 0.41 mmol/liter RBC/hr) was assessed in 185 consecutive insulin-dependent diabetic patients attending an outpatient diabetic clinic. Normoalbuminuria was defined as an overnight albumin excretion rate (AER) of less than 20 micrograms/min (N ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.134
更新日期:1992-04-01 00:00:00
abstract::Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology servic...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2018.10.031
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:The peritoneum is progressively denuded of its mesothelial cell monolayer in patients on continuous ambulatory peritoneal dialysis (CAPD). These alterations of the mesothelium cause membrane dysfunction and progressive peritoneal fibrosis. Integrins regulate cell motility and play an important role in wound ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00772.x
更新日期:2003-02-01 00:00:00
abstract::Intrarenal angiotensin II is increased in kidney diseases independently of plasma angiotensin II and is thought to promote progressive deterioration of renal architecture. Here we investigated the mechanism of enhanced renal angiotensin II generation in kidney glomerular diseases. For this, kidney- or liver-specific a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.453
更新日期:2014-05-01 00:00:00
abstract::Acute kidney injury (AKI) occurs in about half of patients in septic shock and the mortality of AKI with sepsis is extremely high. An effective therapeutic intervention is urgently required. Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that also have pleiotropic actions. They have been report...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000300
更新日期:2006-05-01 00:00:00
abstract::Dialysis providers in the United States may soon be held accountable for their patients' 30-day hospital readmissions. However, few studies have evaluated the timing of readmissions, which determines the window in which dialysis providers could act to prevent readmission. We therefore examined the timing of readmissio...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.03.025
更新日期:2017-10-01 00:00:00
abstract::The kidney is influenced by circadian rhythms and is entrained to the sleep-wake cycle allowing anticipation of the metabolic and physiological demands of the kidney throughout a 24-hour cycle. Although sleep disruption has been studied extensively in cardiovascular and metabolic disease, its association with chronic ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2015.12.048
更新日期:2016-06-01 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::The kinetics of formaldehyde washout in new and reused dialyzers with 2% (w/v) and 4% formaldehyde solution was studied. Using a standard method of rinsing, the concentration of formaldehyde decreases exponentially, but the rate of decrease and the steady-state level depends on the type of dialyzer. The residual quant...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.221
更新日期:1985-12-01 00:00:00
abstract:BACKGROUND:High-dose folinic acid is used to accelerate methotrexate elimination to avoid renal toxicity of the drug. The present study was carried out to examine the role of the renal organic anion transporters OAT-K1 and OAT-K2 in the urinary excretion of methotrexate, especially in the methotrexate-folinic acid resc...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0600031058.x
更新日期:2001-09-01 00:00:00
abstract:BACKGROUND:Aquaporin-2 (AQP-2) proteins are mainly expressed at the apical region of the collecting duct cells. We previously reported three different mutations in the C-terminus of AQP-2 that all-cause autosomal-dominant nephrogenic diabetes insipidus. When one of these mutant AQP-2s was expressed in Madin-Darby canin...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00654.x
更新日期:2005-11-01 00:00:00
abstract:BACKGROUND:Hypertriglyceridemia is a result of reduced triglyceride (TG)-rich lipoprotein (TRL) catabolism and occurs in rats with nephrotic syndrome (NS) and in Nagase analbuminemic rats (NARs). While the heparin-releasable lipoprotein lipase (LpL) pool in NAR and in NS is similar, TG levels are significantly greater ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00478.x
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Advanced glycation end products (AGEs) accumulate in patients with diabetes, particularly at sites of vascular damage and within atherosclerotic lesions, but whether they have direct actions on vascular smooth muscle cells (VSMCs) is controversial. METHODS:AGEs were constructed and characterized by protein ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00746.x
更新日期:2005-12-01 00:00:00
abstract::The X-linked Hyp and Gy mutations are murine homologues of X-linked hypophosphatemia (XLH), a dominant disorder of phosphate (Pi) homeostasis characterized by growth retardation, rickets, hypophosphatemia and decreased renal tubular maximum for Pi reabsorption relative to glomerular filtration rate (Tmp/GFR). In Hyp a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.149
更新日期:1996-04-01 00:00:00
abstract:BACKGROUND:In the rat cortical thick ascending limb (CTAL), intracellular Ca2+ ([Ca2+]i) responses to angiotensin II (Ang II) and angiotensin III (Ang III) were mediated by the Ang II subtype 1A receptor (AT1A-R), whereas the arginine vasopressin (AVP)-dependent cAMP accumulation involved the vasopressin receptor type ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00366.x
更新日期:2002-06-01 00:00:00
abstract::Human renal dysplasia is frequently associated with urinary tract obstruction and the abnormal expression of mitogen-activated protein kinase (MAPK). Here, we determined the renal responses and MAPK expression in developing kidneys that were obstructed in fetal lambs. Kidneys were harvested at various times after obst...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.3
更新日期:2008-05-01 00:00:00
abstract::Disasters result in a substantial number of renal challenges, either by the creation of crush injury in victims trapped in collapsed buildings or by the destruction of existing dialysis facilities, leaving chronic dialysis patients without access to their dialysis units, medications, or medical care. Over the past two...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2013.392
更新日期:2014-05-01 00:00:00
abstract::Intercellular adhesion molecule-1 (ICAM-1) and MHC class II (Ia) antigens are increased on proximal tubular epithelial cells (TEC) in autoimmune nephritis and transplant rejection. ICAM-1 is a member of the immunoglobulin gene superfamily that increases the avidity of T cell interactions with antigen-presenting cells ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.221
更新日期:1990-09-01 00:00:00
abstract::Amyloidosis results from protein misfolding, and ongoing amyloid deposition can ultimately lead to organ failure and death. Historically, this is a group of diseases with limited treatment options and frequently poor prognosis. However, there are now 'targeted' therapeutics emerging in the form of stabilizers of the p...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2014.368
更新日期:2015-03-01 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::Multiple microRNAs (miRs) are implicated in muscle cell differentiation and muscle mass regulation. Pharmacological agents targeting miR-486 and other miRs, involved in muscle mass regulation, could potentially be developed into therapeutic agents for muscle wasting. Muscle wasting is prevalent among patients with chr...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2012.150
更新日期:2012-08-01 00:00:00
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
doi:10.1016/j.kint.2019.01.009
更新日期:2019-07-01 00:00:00