Abstract:
BACKGROUND:Osteogenic protein-1/bone morphogenetic protein-7 (OP-1/BMP-7), a member of the transforming growth factor-beta superfamily, has been shown to prevent kidney damage from ischemia/reperfusion injury in rats. The molecular events involved in OP-1 action on kidney are not yet understood. METHODS:In this study, we evaluated the biodistribution of (125)I-labeled OP-1 in rat kidneys. Adult rats received a single intravenous injection of 250 microg (125)I-labeled OP-1 per kg body wt, a dose that was effective in protecting kidneys from ischemic injury. Tissue localization, in situ hybridization, and immunostaining with a specific receptor antibody were performed to identify OP-1 cellular targets. Also, isolated plasma membranes from kidney cortex and medulla regions were analyzed to identify and characterize receptor structural components that recognize OP-1. RESULTS:At 10 and 180 minutes following injection, the relative uptake of (125)I-labeled OP-1 was consistently higher in kidney cortex than in medulla region. Upon autoradiography, kidney tissue sections revealed that OP-1 bound to the convoluted tubule epithelium, glomeruli, and collecting ducts. Moreover, in situ hybridization and immunostaining methods have shown localization of mRNA transcripts and the protein for BMP receptor type II in the cortex and medulla in similar areas as (125)I-labeled OP-1. Bulk membranes (enriched with plasma membranes) isolated from the cortex and medulla regions of kidney each bound specifically to (125)I-OP-1, and the binding of (125)I-labeled OP-1 was inhibited by unlabeled OP-1 in a dose-dependent manner. However, platelet-derived growth factor, transforming growth factor-beta, insulin-like growth factor, fibroblast growth factors, and other members of BMP family such as BMP-2 and cartilage-derived morphogenetic protein-1/growth and differentiation factor-5 (CDMP-1/GDF-5) failed to inhibit the binding of (125)I-labeled OP-1 to receptors, suggesting a high degree of specificity with which OP-1 bound to kidney receptors. Scatchard analysis of quantitative binding data indicated that the OP-1 receptors of kidney contained a single class of high-affinity binding sites for OP-1 with an association constant (Ka) of 2.26 x 109 mol/L-1 and a binding capacity of 1.01 pmol of OP-1 per mg membrane protein. When analyzed by a ligand blot technique, plasma membranes isolated from kidney cortex and medulla each showed the presence of a prominent specific band with a relative molecular mass (Mr) of 100 kD. Further analysis by Western blotting indicated that an antibody raised against BMP type II receptor effectively recognized the 100 kD OP-1 binding component of kidney plasma membranes. CONCLUSIONS:We demonstrated, to our knowledge for the first time, the presence of membrane-bound, specific, high-affinity OP-1 receptors in rat kidney tissues, which are likely to mediate OP-1 actions in the kidney. The major OP-1-binding component of the kidney appears to be a long form of BMP type II receptor with a Mr of 100 kD. In vivo and in vitro evidence suggests that the cellular targets for OP-1 are convoluted tubule epithelium, glomeruli, and collecting ducts. OP-1 does not share receptor binding properties with other growth factors, including BMP-2 and CDMP-1, suggesting that its mode of action in kidney appears to be specific.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Bosukonda D,Shih MS,Sampath KT,Vukicevic Sdoi
10.1111/j.1523-1755.2000.00362.xsubject
Has Abstractpub_date
2000-11-01 00:00:00pages
1902-11issue
5eissn
0085-2538issn
1523-1755pii
S0085-2538(15)47298-9journal_volume
58pub_type
杂志文章abstract:BACKGROUND:Regular access monitoring is recommended to detect and treat access stenosis in order to prevent access thrombosis and failure. METHODS:In 1999, we instituted monthly access blood flow monitoring using the ultrasound dilution technique (UDT). In a sequential observational trial, 222 patients were studied fo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00697.x
更新日期:2005-11-01 00:00:00
abstract::Apoptosis mediated by verotoxins (VTs) has been identified in a renal carcinoma cell line, ACHN cells, which are an in vitro model of renal tubular epithelial cells. ACHN cells express the renal tubular marker CD24 as well as globotriaosyl ceramide/CD77, the receptor for VTs. VT binding to the ACHN cell surface was co...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00939.x
更新日期:1998-06-01 00:00:00
abstract::IgA nephropathy is the most common primary glomerulonephritis worldwide. Its frequent coexistence with inflammatory, infectious, or malignant processes raises the possibility of a pathologic rather than coincidental association. Major strides have been made to elucidate the underlying pathophysiologic events that culm...
journal_title:Kidney international
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doi:10.1016/j.kint.2018.02.030
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abstract::The present study was undertaken to: (a) clarify the comparative renal potency of bolus injection of the natriuretic peptides urodilatin and ANF99-126 in the rat; (b) establish whether or not intravenous (i.v.) infusion of urodilatin (200 ng/min) combined with dopamine (UD) to maintain mean arterial pressure could imp...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.399
更新日期:1992-11-01 00:00:00
abstract:BACKGROUND:Primary collapsing glomerulopathy recurs postransplant, raising the possibility of circulating factors implicated in the pathogenesis of the disease. METHODS:To determine the presence of circulating factors in collapsing glomerulopathy patients, we tested serum from those patients in an in vivo assay. Eleve...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00715.x
更新日期:2004-07-01 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:BACKGROUND:Although several kinds of evidence suggest that glycosaminoglycans (GAGs) and proteoglycans (PGs) may contribute to the development of beta2-microglobulin-related (Abeta2m) amyloidosis, the precise roles of these molecules for the development of Abeta2m amyloidosis are poorly understood. METHODS:We investig...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00167.x
更新日期:2003-09-01 00:00:00
abstract:BACKGROUND:Low dietary phosphorus (P) prevents parathyroid gland (PTG) hyperplasia and the development of secondary hyperparathyroidism (SH) in uremic rats. The present study explores the effects of P restriction on parathyroid hormone (PTH) synthesis and secretion and PT cell growth in rats with established SH and PTG...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00265.x
更新日期:2002-04-01 00:00:00
abstract::We have analyzed the protein content of proximal tubular fluid (PTF) by ultramicro disc electrophoresis and measured total protein excretion rates both in control conditions and during angiotensin infusion to the rat. Under control conditions PTF albumin concentration was 1.49 +/- 1.12 (SD) mg/100 ml and did not incre...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.83
更新日期:1975-08-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1997.201
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00141.x
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00166.x
更新日期:2002-02-01 00:00:00
abstract::The primary hyperoxalurias are diseases of overproduction of oxalate. The immediate precursor of oxalate is glyoxylate. Metabolism of hydroxyproline, derived from collagen turnover or the diet, appears to be a major source of glyoxylate, and a potential target for a therapeutic strategy of substrate depletion. ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5001987
更新日期:2006-12-01 00:00:00
abstract::The relationship between commonly occurring genetic variants (G1 and G2) in the APOL1 gene in African Americans and different disease traits, such as kidney disease, cardiovascular disease, and pre-eclampsia, remains the subject of controversy. Here we took a genotype-first approach, a phenome-wide association study, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.01.027
更新日期:2020-05-01 00:00:00
abstract::The possibility that hypercalciuria could cause calcium stone formation through a mechanism other than by increasing urinary saturation of stone-forming calcium salts was explored. The effect of increasing calcium concentration on the inhibitor activity against the spontaneous precipitation of calcium oxalate was exam...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.100
更新日期:1988-05-01 00:00:00
abstract::Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase. Its activation results in beneficial or detrimental consequences, depending on the particular setting. Earlier studies in the animal model of acute kidney injury showed that EGFR activation promotes renal tubular cell proliferation. Activation of E...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2012.435
更新日期:2013-05-01 00:00:00
abstract::In recent times, therapy for renal anemia has changed dramatically in that iron administration has increased and doses of erythropoiesis-stimulating agents (ESAs) have decreased. Here we used a prospective, observational, multicenter design and measured the serum ferritin and hemoglobin levels every 3 months for 2 yea...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1038/ki.2014.114
更新日期:2014-10-01 00:00:00
abstract::A substantial body of evidence has accumulated linking an increased incidence of cardiovascular disease in patients with acute kidney injury (AKI), chronic kidney disease (CKD), and end-stage renal disease (ESRD). A multitude of novel risk factors related to decreased kidney function might interact with the renal and ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2011.178
更新日期:2011-09-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1046/j.1523-1755.2001.00985.x
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journal_title:Kidney international
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.144
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.154
更新日期:2013-09-01 00:00:00
abstract::Healthy male rats were exposed to a chronic ingesta of an isotonic NaCl solution during a period of four months. Two different preparations were utilized to study the effect of this treatment on the active mechanisms of Na+ reabsorption of kidney proximal tubular cells: outermost kidney cortex slices (rich in proximal...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.216
更新日期:1986-10-01 00:00:00
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journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.327
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:Pre-eclampsia is characterized by hypertension, proteinuria and edema. Simultaneous studies of kidney function and structure have not been reported. We wished to explore the degree and nature of glomerular dysfunction in pre-eclampsia. METHODS:Physiologic techniques were used to estimate glomerular filtrati...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00097.x
更新日期:1998-10-01 00:00:00
abstract::The cardiorenal safety database from the Celecoxib Long-term Arthritis Safety Study (CLASS) was analyzed to examine whether supratherapeutic doses of celecoxib are associated with decreased renal function and blood pressure (BP) effects compared with standard doses of diclofenac and ibuprofen in osteoarthritis (OA) an...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.ki.5001766
更新日期:2006-10-01 00:00:00
abstract::Residual kidney function (RKF) may confer a variety of benefits to patients on maintenance dialysis. RKF provides continuous clearance of middle molecules and protein-bound solutes. Whereas the definition of RKF varies across studies, interdialytic urine volume may emerge as a pragmatic alternative to more cumbersome ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2016.02.037
更新日期:2016-08-01 00:00:00
abstract:BACKGROUND:Wegener's granulomatosis (WG) is a rare systemic autoimmune disease characterized by small-vessel vasculitis leading to organ damage and the presence of antineutrophil cytoplasmic autoantibodies (ANCAs). ANCAs were shown to be involved in the pathogenesis of the disease by increasing adhesion of polymorphonu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00430.x
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND:Tacrolimus is a relatively new calcineurin inhibitor that has been increasingly used in transplant medicine. The objective of the current work is to report our preliminary experience with tacrolimus in the treatment of diffuse proliferative glomerulonephritis in systemic lupus erythematosus (SLE). METHODS:N...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
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更新日期:2005-08-01 00:00:00