Abstract:
:To analyze the role of clusterin in renal diseases involving a regenerative process, we have used a novel rodent model to compare temporal and spatial expression of clusterin mRNA. Thus, renal artery stenosis was used to induce unilateral non-infarctive renal atrophy. After several weeks, when cellular pathology of atrophic kidneys involved minimal apoptosis or inflammatory response and mitosis was at normal levels, regeneration of atrophic kidneys was stimulated by removal of the contralateral healthy kidneys. The regrowth response was very rapid and involved renal hyperplasia rather than hypertrophy. Regenerating kidneys were studied 0, 4, 8, 24 hours and 2, 3, 5, 7, and 14 days after contralateral nephrectomy. Several parameters were compared: level and localization of clusterin mRNA; cell proliferation; cell dedifferentiation and redifferentiation and apoptosis. During the acute regenerative phase (first 24 hr) clusterin expression was markedly increased, decreasing to untraceable levels by five days of regeneration. Clusterin mRNA was localized in dilated or collapsed atrophic tubules that had lost identifying surface structures of normal tubular epithelium (termed dedifferentiated). Clusterin was also localized in the periphery of some blood vessel walls. Cell proliferation peaked at three to five days of regeneration, and was also localized in dedifferentiated tubules. Despite the regenerative stimulus, an unexpected result was a transient but marked increase in apoptotic cell death in atrophic tubules in the first 24 hours of regeneration. Our results provide evidence of a temporal association between increased clusterin expression and apoptosis, but in situ localization showed clusterin mRNA over apparently viable, as well as apoptotic, cells in the epithelium of tubules showing clusterin expression. Clusterin mRNA was rarely identified over epithelial cells in foci of non-atrophic (non-dedifferentiated) nephrons that responded to the regenerative stimulus by cellular hypertrophy. The dramatic response after initiation of regeneration, especially the initiation of apoptosis in the tubular epithelium, may have applications for the study of genetic changes leading to renal oncogenesis.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Gobé GC,Buttyan R,Wyburn KR,Etheridge MR,Smith PJdoi
10.1038/ki.1995.54subject
Has Abstractpub_date
1995-02-01 00:00:00pages
411-20issue
2eissn
0085-2538issn
1523-1755pii
S0085-2538(15)58818-2journal_volume
47pub_type
杂志文章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: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:BACKGROUND:Prolactin (PRL), originally identified as an anterior pituitary hormone exhibiting lactogenic activity, is now recognized as a versatile hormone expressed in a wide variety of tissues. METHODS:In this study, the expression of PRL in the mouse kidney was investigated by solution-phase and in situ reverse tra...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.055003833.x
更新日期:1999-03-01 00:00:00
abstract::Previous studies have shown that nonsteroidal anti-inflammatory drug (NSAID) use might be associated with a lower risk of developing cancer in the general population. Patients on dialysis have increased risk for cancer, but there are no studies to determine the relationship between NSAID use and cancer risk in these p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.79
更新日期:2013-07-01 00:00:00
abstract::Diabetic nephropathy is a growing health concern with characteristic sterile inflammation. As the underlying mechanisms of this inflammation remain poorly defined, specific therapies targeting sterile inflammation in diabetic nephropathy are lacking. Intriguingly, an association of diabetic nephropathy with inflammaso...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.271
更新日期:2015-01-01 00:00:00
abstract::Previous studies have shown a number of different associations between major histocompatibility complex (MHC) alleles and primary systemic vasculitis. Disease heterogeneity and the lack of specificity of certain MHC typing techniques may have contributed to the lack of consistency in those studies. We therefore studie...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.37
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND:Tumor necrosis factor (TNF) receptor family members, such as Fas and TNF receptor 1 (TNFR1), are thought to induce apoptosis in a variety of cells and organs. Although a number of potential scenarios have been postulated for the involvement of these receptors in the pathogenesis of acute renal failure (ARF),...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00709.x
更新日期:2003-01-01 00:00:00
abstract::Activation of cAMP signaling pathway was shown to inhibit some pathobiologic processes in mesangial cells (MC). We investigated whether adrenomedullin (ADM), a potent agonist of adenylate cyclase, is synthesized in MC and whether it can, via cAMP, suppress the generation of reactive oxygen metabolites (ROM) and prolif...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.413
更新日期:1997-10-01 00:00:00
abstract::Ischemia-reperfusion injury (IRI) is the outcome of an inflammatory process that is triggered when an organ undergoes a transient reduction or cessation of blood flow, followed by re-establishment of perfusion. In the clinical setting, IRI contributes to significant acute kidney injury, patient morbidity and mortality...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2019.02.009
更新日期:2019-08-01 00:00:00
abstract::Chronic kidney disease (CKD) has received increased attention as a leading public health problem worldwide. Globally surveillance systems for kidney disease are still lacking, especially in developing countries like China, which constitutes an obstacle to develop effective preventive strategies. China Kidney Disease N...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.11.011
更新日期:2019-03-01 00:00:00
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
doi:10.1038/ki.2012.412
更新日期:2013-03-01 00:00:00
abstract::As new components of the renin-angiotensin system (RAS) are elucidated, our understanding of the complexities of their interactions also advances. Previous studies have determined that podocytes possess a local RAS that can generate angiotensin II. Podocytes have also been shown to express angiotensin-converting enzym...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2012.127
更新日期:2012-08-01 00:00:00
abstract::Acute kidney injury (AKI) is a critical condition with a mortality rate as high as 50% and significantly contributes to the burden of end-stage renal disease (ESRD) requiring renal replacement therapy. The incidence and prognosis of AKI have been shown to vary with patient age, with younger individuals being more resi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.394
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND:The ontogeny of the renal mineralocorticoid (MR) and glucocorticoid (GR) receptors in the ovine fetus, and the effects of early exposure to synthetic or natural glucocorticoids on the expression of these genes in late gestation were examined. METHODS:A partial cDNA sequence for the ovine MR was cloned and u...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00157.x
更新日期:2002-02-01 00:00:00
abstract::During online hemodiafiltration, patients are directly infused with sterile substitution solutions to maintain fluid balance. Adequate water treatment and a well-organized quality control process are essential to provide non-pyrogenic fluids with consistent optimal quality. We sought to assess water quality, the water...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.245
更新日期:2009-09-01 00:00:00
abstract::Vascular calcification is prevalent in dialysis patients and is associated with a high burden of cardiovascular disease. Fetuin-A is a potent inhibitor of vascular calcification, but the precise mechanism by which it mediates vascular calcification in uremia is unclear. Matsui and colleagues demonstrate that circulati...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2009.52
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:Cell membranes and their lipids play critical roles in calcification. Specific membrane phospholipids promote the formation of calcium phosphate and become a part of the organic matrix of growing calcification. We propose that membrane lipids also promote the formation of calcium oxalate (CaOx) and calcium p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00676.x
更新日期:2002-12-01 00:00:00
abstract::Factor H is a regulator of the alternative pathway of complement, and genetic studies have shown that patients with mutations in factor H are at increased risk for several types of renal disease. Pathogenic activation of the alternative pathway in acquired diseases, such as ischemic acute kidney injury, suggests that ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.115
更新日期:2011-07-01 00:00:00
abstract:BACKGROUND:Redox-active iron can promote oxidative stress and tissue injury by catalyzing hydroxyl radical generation and lipid peroxidation. Intravenous iron preparations are routinely administered in conjunction with erythropoietin to treat anemia in patients with chronic renal failure (CRF), a condition that is mark...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00580.x
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND:We aimed to identify genes with kidney specific, developmentally regulated expression. Here we report the cDNA sequence and expression pattern of KS, a novel kidney-specific rat gene. METHODS:A partial cDNA was identified by differential display polymerase chain reaction (PCR) of a renal cell fraction enric...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00143.x
更新日期:1998-11-01 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::The transforming growth factor-beta (TGF-beta) plays a central role in the progression of renal fibrosis. TGF-beta transduces its signal through the activin receptor-like kinase (ALK)5. IN-1130, a novel small molecule ALK5 inhibitor, inhibited the purified kinase domain of ALK5-mediated Smad3 phosphorylation with an I...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001775
更新日期:2006-10-01 00:00:00
abstract:BACKGROUND:Bicarbonate reabsorption in the kidney proximal tubule is predominantly mediated via the apical Na+/H+ exchanger (NHE-3) and basolateral Na+: HCO(-3) cotransporter (NBC-1). The purpose of these studies was to examine the effects of Na+ load and altered acid-base status on the expression of NHE-3 and NBC-1 in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00995.x
更新日期:2001-11-01 00:00:00
abstract::Kallistatin is a serine protease inhibitor with anti-inflammatory, anti-angiogenic, and anti-oxidative properties. Since oxidative stress plays a critical role in the pathogenesis of diabetic nephropathy, we studied the effect and mechanisms of action of kallistatin superinduction. Using ultrasound-microbubble-mediate...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.331
更新日期:2016-02-01 00:00:00
abstract:BACKGROUND:Tissue kallikrein regulates blood circulation. Low urinary kallikrein excretion was associated with hypertension and renal disease in blacks. The polymorphic KLK1 promoter includes -130 GN coupled with multiple single base substitutions. The -130 G12 allele in the KLK1 promoter was associated with lower tran...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00526.x
更新日期:2004-04-01 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::Progranulin (PGRN), an autocrine growth factor, has multiple physiological functions and is widely involved in the pathogenesis of many types of diseases. The pivotal anti-inflammatory function of PGRN in rheumatoid arthritis encouraged us to examine the role of PGRN in acute kidney injury (AKI). We found that levels ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.403
更新日期:2015-05-01 00:00:00
abstract::Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI) when used in triple combination with renin-angiotensin system inhibitors and diuretics, but previous research reported that NSAIDs in dual combinations with either renin-angiotensin system inhibitors or diu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.101
更新日期:2015-08-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) are key mediators of adverse peritoneal membrane remodeling in peritoneal dialysis eventually leading to ultrafiltration failure. Both are pleiotropic growth factors with cell type-dependent regulation of expression and biological eff...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.217
更新日期:2013-12-01 00:00:00
abstract::Cell surface aminopeptidases N (APN) and A (APA) have been characterized on cultured human glomerular epithelial cells and a SV40-transformed cell line derived from them. APN had a wide substrate specificity whereas APA only attacked peptides with an acidic N terminal amino acid. Both enzymes also differed by their se...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.227
更新日期:1992-06-01 00:00:00