Abstract:
BACKGROUND:The biologic responses to transforming growth factor-beta (TGF-beta) suggest many potential therapeutic applications; however, in the only clinical trial to examine the effect of the systemic administration of a TGF-beta isoform, patients experienced significant but reversible declines in renal function. We studied the effects of administering human recombinant TGF-beta2 to adult mice. METHODS:The effect of daily administration of TGF-beta2 on tissue vasoconstriction, tissue levels of endothelin and angiotensin II, tissue hypoxia, and renal fibrosis were examined. RESULTS:Daily administration of TGF-beta2 at 10 or 100 microg/kg caused apparent tissue vasoconstriction that was visualized by vascular casting, with the largest impact seen in the kidney. Tissue levels of endothelin 1 and angiotensin II were significantly elevated in kidneys of treated mice, as was urinary thromboxane beta2. Renal fibrosis was observed in the cortical tubular interstitium and vasculature, particularly at the cortical-medullary junction and medullary vasa recta; however, glomerular sclerosis was not observed. Fibrosis was correlated to focal tissue hypoxia as determined by immunohistochemical detection of tissue bound pimondazole. CONCLUSION:We conclude that there are significant histopathologic consequences, focused in the kidney, resulting from the daily administration of high doses of human recombinant TGF-beta2, and we propose that selective vascular constriction with consequent tissue hypoxia is a contributing factor.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Ledbetter S,Kurtzberg L,Doyle S,Pratt BMdoi
10.1046/j.1523-1755.2000.00420.xsubject
Has Abstractpub_date
2000-12-01 00:00:00pages
2367-76issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(15)47353-3journal_volume
58pub_type
杂志文章abstract::Loss of hypoxic vasodilation has been proposed as a causative factor in the development of hypertension in dialysis patients treated with recombinant human erythropoietin (rHuEPO). Venous occlusion plethysmography was therefore performed on 22 dialysis patients (aged 23 to 71 years, dialysis duration 6 to 260 months, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.376
更新日期:1992-10-01 00:00:00
abstract::Proteinuric diabetic patients have an increased risk of cardiovascular disease and almost always have hypertension. In the early stages of diabetic renal disease (microalbuminuria) when renal function is well preserved, systemic arterial blood pressure is already elevated compared to insulin-dependent diabetic patient...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1994.56
更新日期:1994-02-01 00:00:00
abstract::Arguably, no cell biology related to the loss of renal function is more debated than the ontogeny of fibrosis in the kidney. Recent studies suggest that the fibroblasts depositing most of the excess extracellular matrix in diseased kidneys derive from epithelial cells versus pericytes resident within the kidney. Reich...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.107
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:Podocytes are highly differentiated glomerular epithelial cells with limited potential to divide. They are responsible for maintaining and supporting the glomerular basement membrane so as to facilitate efficient filtration. The hypothesis tested was whether the development of glomerulosclerosis in the purom...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.060003957.x
更新日期:2001-09-01 00:00:00
abstract::Risk factors for disease states are rigorously defined. This analysis considers the definition of a risk factor as applied to the question of whether the serum phosphorus level is a risk factor for cardiovascular disease. Observational studies strongly suggest that phosphorus is associated with cardiovascular risk, an...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2011.24
更新日期:2011-04-01 00:00:00
abstract::A protective role for sirtuin 6 (Sirt6) in the context of chronic renal injury is reported by Cai et al. in this issue of Kidney International. The mechanism is thought to be mediated by Sirt6's deacetylase activity, specifically on β-catenin target genes. This commentary discusses these results and the interaction be...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2019.09.022
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Rats that recover from acute puromycin nephrosis later develop widespread glomerular and tubulointerstitial injury. The current study sought to identify structural changes present in the recovery phase that could precipitate progressive renal disease. METHODS:Stereologic studies were performed 10 weeks afte...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00481.x
更新日期:2002-08-01 00:00:00
abstract:BACKGROUND:A considerable diversity in prognosis is seen with lupus glomerulonephritis (LGN). Hence, the clinical usefulness of a recent International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification to judge the long-term outcome of human LGN has been investigated. METHODS:We studied retros...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.66027.x
更新日期:2004-12-01 00:00:00
abstract::The use of the immuno-suppressant cyclosporine A (CsA) after transplantation has been associated with less favorable plasma lipid profiles, which may contribute to the high incidence of cardiovascular morbidity and mortality in transplant recipients. Recent studies have suggested that oxidative modification of LDL pla...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1997.221
更新日期:1997-05-01 00:00:00
abstract:BACKGROUND:Intrauterine growth retardation (IUGR) is associated with higher morbidity and mortality not only in perinatal life but also in later life. The purpose of our study was to determine whether IUGR has any effect on the course of minimal change nephrotic syndrome (MCNS) in children. METHODS:Forty children who ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00121.x
更新日期:1998-10-01 00:00:00
abstract::Zhang and co-workers report on the renoprotective role of the vitamin D receptor (VDR) in diabetic nephropathy using the method of streptozotocin-induced hyperglycemia in wild-type and VDR(-/-) mice. Also, experiments with cultured mesangial cells and podocytes confirm the effect of the active vitamin D metabolite 1,2...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002693
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Among the members of the small leucine-rich proteoglycan family, decorin, biglycan, and fibromodulin have been proposed to be potent modulators of transforming growth factor-beta (TGF-beta) activity, thereby playing an important role in the pathogenesis of fibrotic kidney diseases. Furthermore, decorin expre...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00317.x
更新日期:2000-10-01 00:00:00
abstract::The antiphospholipid syndrome is a common autoimmune disease caused by pathogenic antiphospholipid antibodies, leading to recurrent thrombosis and/or obstetrical complications. Importantly for nephrologists, antiphospholipid antibodies are associated with various renal manifestations including large renal vessel throm...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2016.06.026
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Bone marrow reconstitution using genetically-modified hematopoietic stem cells has been reported to confer resistance to inflammation and prevent renal injury in glomerulonephritis. Although this strategy has potentials for clinical use, taking hematopoietic stem cells from bone marrow is highly stressful fo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00046.x
更新日期:2003-07-01 00:00:00
abstract::Cytokines are important modulators of inflammation. The balance between pro- and anti-inflammatory cytokines determines whether the intensity of inflammatory response is within physiological limits or in the pathological range. The cytokine network is highly complex, containing interactive cascades of gene activation ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002391
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:The inhibitor of apoptosis (IAP) family of proteins regulates programmed cell death triggered by various stimuli. The purpose of this investigation was to examine the expression, regulation, and function of IAP genes in cultured rat mesangial cells. METHODS:Basal and inducible expression of c-IAP1, c-IAP2, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.060002579.x
更新日期:2001-08-01 00:00:00
abstract::Obesity could affect associations between creatinine generation, estimated body surface area, and excretory burden, with effects on chronic kidney disease assessment. We therefore examined the impact of obesity on the performances of estimated glomerular filtration rate (eGFR), the urine albumin:creatinine ratio (ACR)...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.112
更新日期:2014-12-01 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::Medial arterial calcification involves chondrogenic/osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Zhao et al. report that phosphate activates the mammalian target of rapamycin (mTOR) cascade in VSMCs, leading to downregulation of Klotho. Furthermore, rapamycin was shown to halt medial calcif...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2015.223
更新日期:2015-10-01 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:BACKGROUND:Microarray technology is a powerful tool that can probe the molecular pathogenesis of renal injury. In this present study microarray analysis was used to monitor serial changes in the renal transcriptome of a rat model of mesangial proliferative glomerulonephritis. Administration of anti-Thy1 antibody result...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00661.x
更新日期:2005-12-01 00:00:00
abstract::Diabetic kidney disease is the leading cause of kidney failure. However, studies of molecular mechanisms of early kidney damage are lacking. Here we examined for possible linkage between transcriptional regulation and quantitative structural damage in early diabetic kidney disease in Pima Indians with type 2 diabetes....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.08.013
更新日期:2018-02-01 00:00:00
abstract::E-64d, a membrane-permeable cysteine protease inhibitor, was tested for its ability to inhibit PTH-induced contraction in intact mouse MC-3T3-E1 osteoblastic cells. Incubation of MC-3T3-E1 cells with vehicle (DMSO) or E-64c, a nonpermeant cysteine protease inhibitor, in the presence or in the absence of PTH had no eff...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.99
更新日期:1993-03-01 00:00:00
abstract::The content of platelet activating factor (PAF) in glomeruli isolated from rats with nephrotoxic serum glomerulonephritis (NSGN) was quantified at various stages of the disease and the role of complement, platelets and neutrophils in mediating changes in glomerular PAF levels was evaluated. PAF content was assessed fo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.40
更新日期:1990-02-01 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:BACKGROUND:Cux-1 is a murine homeobox gene that is highly expressed in the nephrogenic zone of the developing kidney. Transgenic mice ectopically expressing Cux-1 develop renal hyperplasia associated with down-regulation of the cyclin kinase inhibitor p27. Because the reduction of p27 has been associated with mesangial...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00889.x
更新日期:2003-04-01 00:00:00
abstract::Fourteen subjects with persistent azotemia and normal glomerular filtration rate were studied by renal clearances and hormonal determinations to establish the nephron site of altered urea transport and the mechanism(s) responsible for their azotemia. During constant alimentary protein, urea nitrogen appearance was nor...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.266
更新日期:1987-11-01 00:00:00
abstract::The neonatal proximal tubule has a lower rate of bicarbonate absorption than that of adults. This is due, in part, to a lower rate of apical membrane Na+/H+ antiporter activity. The purpose of these studies was to examine if thyroid hormone could be a factor in the maturational increase in Na+/H+ antiporter activity. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00879.x
更新日期:1998-05-01 00:00:00
abstract::Renal dysfunction is a common and serious complication in multiple myeloma (MM) patients. Renal proximal tubule injury is characteristic in MM, and may result in disturbed renal handling of various vitamins. The abnormal excretion of vitamins in urine may result in their low serum levels. The goal of this study was to...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000024
更新日期:2006-01-01 00:00:00
abstract::Insulin and growth factors activate the phosphatidylinositide-3-kinase pathway, leading to stimulation of several kinases including serum- and glucocorticoid-inducible kinase isoform SGK3, a transport regulating kinase. Here, we explored the contribution of SGK3 to the regulation of renal tubular phosphate transport. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.67
更新日期:2011-07-01 00:00:00