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 proliferation of cells in glomeruli. With the use of an immunohistologic technique ADM was detected in mesangial and microvascular areas of rat glomeruli. MC grown in primary culture synthesized ADM, and the synthesis was stimulated by TNF alpha and IL-1 beta but not by PDGF and EGF. ADM inhibited ROM generation in MC dose-dependently and caused in situ activation of protein kinase A (PKA). In macrophages (cell line J774) ROM generation was about four times higher than in MC and was inhibited by ADM in a similar way as in MC. The rate of MC proliferation, measured by [3H]-incorporation, and the activity of mitogen-activated protein kinase (MAPK) stimulated by PDGF and EGF were dose-dependently inhibited by ADM; the maximum inhibition (at 10 nM ADM) was about -80%. Mitogenesis of MC and MAPK activity when stimulated to a similar extent by endothelin (ET-1) was inhibited by ADM to a significantly (P < 0.01) lesser degree (-30%). Further, ADM inhibited PDF-stimulated mitogenesis and activation of MAPK in cultured vascular smooth muscle cells (VSMC). The inhibition of PDGF-activated MAPK by ADM in VSMC was reversed by the protein kinase A (PKA) inhibitor, H89. Taken together, results indicate the adrenomedullin (ADM) generated in mesangial cells (MC) can suppress, via activation of the cAMP-protein kinase A (PKA) signaling pathway, reactive oxygen metabolites (ROM) generation in MC and infiltrating macrophages as well as mitogen-activated protein kinase (MAPK)-mediated mitogenesis in MC and vascular smooth muscle cells (VSMC). We suggest that introglomerular ADM may serve as a cytoprotective autoacoid that suppresses pathobiologic processes evoked by immuno-inflammatory injury of glomeruli.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Chini EN,Chini CC,Bolliger C,Jougasaki M,Grande JP,Burnett JC Jr,Dousa TPdoi
10.1038/ki.1997.413subject
Has Abstractpub_date
1997-10-01 00:00:00pages
917-25issue
4eissn
0085-2538issn
1523-1755pii
S0085-2538(15)60253-8journal_volume
52pub_type
杂志文章abstract:BACKGROUND:Cisplatin (CP) induced polyuria in rats is associated with a reduction in medullary hypertonicity, normally generated by the thick ascending limb (TAL) salt transporters, and the collecting duct urea transporters (UT). To investigate the molecular basis of this abnormality, we determined the protein abundanc...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00048.x
更新日期:2001-12-01 00:00:00
abstract::Intravital multiphoton microscopy is a powerful tool to study kidney physiology in living animals. However, certain technical issues have curbed its usage to date, including limited depth of tissue penetration and high background emission of endogenous signals. Most previous studies have used the excitation range 700–...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.323
更新日期:2016-03-01 00:00:00
abstract::The relationship between leukopenia and the complement system during hemodialysis was re-examined by studying not only the in vivo effects of four different dialyzer membranes (cellulose hydrate, cuprophan, cellulose acetate, and polyacrilonitrile) on leukocyte counts and complement levels, but especially by investiga...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1983.227
更新日期:1983-12-01 00:00:00
abstract::Acute urinary obstruction causes interstitial inflammation with leukocyte accumulation and the secretion of soluble mediators. Here we show that unilateral ureteral ligation caused a progressive increase in renal F4/80(+) and F4/80(-) dendritic cells, monocytes, neutrophils and T-cells 24-72 h following obstruction. D...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.394
更新日期:2008-11-01 00:00:00
abstract::To investigate mechanisms underlying GFR control in diabetes mellitus, renal hemodynamics and segmental tubular handling of sodium, using lithium clearance, were assessed in 41 insulin-dependent diabetics (IDD) treated by insulin for 11 +/- 8 days, and in 19 normal controls. Average GFR and effective renal plasma flow...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.95
更新日期:1990-04-01 00:00:00
abstract::Hypertension is associated with an accelerated rate of decline in renal function in patients with chronic renal disease. To identify factors that might alter the rate of decline in renal function, we reviewed records of 200 patients from the Nephrology Clinic of the Durham VA Medical Center who had chronic progressive...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.93
更新日期:1990-04-01 00:00:00
abstract:BACKGROUND:Fractalkine is a newly identified T-cell and monocyte/macrophage (Mphi) chemokine with a transmembrane domain and is a cell-surface protein on activated endothelium. It can mediate adhesion of cells expressing the fractalkine receptor CX3CR1. These unique features make fractalkine well suited for leukocyte r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00604.x
更新日期:1999-08-01 00:00:00
abstract::The relative importance of sarcopenia and its individual components as independent predictors of mortality in the dialysis population has not been determined. We estimated whole-body muscle mass using pre-dialysis bioimpedance spectroscopy measurements in 645 ACTIVE/ADIPOSE-enrolled prevalent hemodialysis patients fro...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2017.01.024
更新日期:2017-07-01 00:00:00
abstract:BACKGROUND:Prolonged antihypertensive therapy might be less effective in reversing the left ventricular hypertrophy (LVH) in uremics bearing the deleted (DD) allele of the angiotensin converting enzyme (ACE) gene than in patients with the inserted (II) allele or in those heterozygous (ID) for the gene. METHODS:Thirtee...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00027.x
更新日期:1998-08-01 00:00:00
abstract::The renal handling of gentamicin in the rat was examined by clearance, microinjection, and renal cortical-slice techniques. The steady-state renal clearance of 14C-gentamicin, when corrected for the 7.5% binding to plasma protein, was not significantly different from that of 3H-inulin. At the end of the renal clearanc...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1979.149
更新日期:1979-10-01 00:00:00
abstract::In vitro metabolic acidosis (Met) induces greater bone mineral resorption than respiratory acidosis (Resp). Met, but not Resp, inhibits osteoblasts which control many aspects of osteoclastic function. To determine whether at a similar decrement in extracellular pH, Met and Resp would induce different changes in intrac...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.247
更新日期:1995-06-01 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:BACKGROUND:The debate on the association between nonphenacetin-containing combined analgesics and renal disease has lasted for several years. METHOD:A peer review committee of scientists, selected jointly by the regulatory authorities of Germany, Switzerland, and Austria and the pharmaceutical industry was asked to cr...
journal_title:Kidney international
pub_type: 共识发展会议,杂志文章,评审
doi:10.1046/j.1523-1755.2000.00410.x
更新日期:2000-12-01 00:00:00
abstract::Here we studied a possible association between low parathyroid hormone (PTH) status and mortality in incident patients undergoing hemodialysis . A total of 1983 patients were included at baseline and prospectively followed for 24 months. Patients were classified according to their Kidney Disease: Improving Global Outc...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2015.12.001
更新日期:2016-03-01 00:00:00
abstract::Scavenger receptor A (SR-A) is a key transmembrane receptor in the endocytosis of lipids and contributes to the pathogenesis of atherosclerosis. To assess its role in hyperlipidemic chronic kidney disease, wild-type and SR-A-deficient (knockout) mice underwent uninephrectomy followed by either normal or high-fat diet....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.457
更新日期:2012-05-01 00:00:00
abstract::The kidney is a likely source for some urinary epinephrine (E) since adrenalectomized animals and humans continue to excrete urinary E and the human kidney contains E synthesizing enzymes. We studied subjects during an intravenous infusion of 3H-E to determine the fraction of urinary E derived from the kidney. Eight n...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.40
更新日期:1997-01-01 00:00:00
abstract::Vascular calcification is recognized as a major contributor to cardiovascular disease (CVD) in end stage renal disease (ESRD) patients. Susceptibility to vascular calcification is genetically determined and actively regulated by diverse inducers and inhibitors. One of these inducers, hyperphosphatemia, promotes vascul...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2008.644
更新日期:2009-05-01 00:00:00
abstract::Clofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR alpha) agonist, increases renal tubular cytochrome P450 4a (Cyp4a) expression thereby increasing 20-hydroxyeicosatetraenoic acid (20-HETE) production. To determine if clofibrate affects blood pressure regulation we studied mice with DOCA-salt induced...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.300
更新日期:2008-10-01 00:00:00
abstract::Vascular calcification (VC) is an important reason for the high burden of vascular disease among chronic dialysis patients. Chronic kidney disease (CKD) is associated with increased promoters and decreased inhibitors of VC. The circulating levels of fetuin-A, a well-described inhibitor of calcification, regulate the c...
journal_title:Kidney international
pub_type: 评论,杂志文章,评审
doi:10.1038/sj.ki.5002355
更新日期:2007-07-01 00:00:00
abstract::We studied the specific binding of radiolabeled bradykinin ([3H]BK) and vasopressin ([3H]AVP) to membrane preparations of bovine and porcine kidney medulla. [3H]BK reversibly labeled a single site (Kd = 1.06 nM) in bovine kidney medulla independently of [Mg2+]. The number of BK receptors in bovine kidney medulla, Bmax...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.353
更新日期:1996-08-01 00:00:00
abstract:BACKGROUND:Autosomal-dominant medullary cystic kidney disease (ADMCKD), a hereditary chronic interstitial nephropathy, recently attracted attention because of the cloning or mapping of certain gene loci, namely NPHP1, NPHP2 and NPHP3 for familial juvenile nephronophthisis (NPH) and MCKD1 and MCKD2 for the adult form of...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2002.kid581.x
更新日期:2002-10-01 00:00:00
abstract::The aging process in humans and in the rat is associated with an impairment in renal tubular reabsorption of Pi and renal tubular adaptation to a low Pi diet. The purposes of the present study were to determine whether changes in the abundance of type II Na-Pi contransporter (NaPi-2) protein and/or mRNA play a role in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.385
更新日期:1996-09-01 00:00:00
abstract:BACKGROUND:Angiotensin type 1 (AT1) receptor-deficient mice (Agtr1-/-), which selectively lack both AT1A and AT1B receptor genes, are characterized by marked intrarenal vascular thickening. In the present study, we explored the possible involvement of the kinin-kallikrein system in the development of this renal vascula...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00574.x
更新日期:1999-08-01 00:00:00
abstract::Transient renal tubular acidosis may complicate acute renal failure (ARF). To clarify this phenomenon, the present study examined tubular H+ ion secretory capacity in an ischemic model of ARF. Clearance studies were performed in dogs subjected to 60 minutes, unilateral renal artery clamping. The contralateral kidney s...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.271
更新日期:1986-12-01 00:00:00
abstract::When patients develop acute kidney injury, a small fraction of them will develop end-stage renal disease later. The severity of renal impairment in the remaining patients is uncertain because studies have not carefully examined renal function over time or the precise timing of entry into a late stage of chronic kidney...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.332
更新日期:2009-11-01 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::Our previous in vivo study demonstrated that methylprednisolone (MP) activates glomerular antioxidant enzymes and attenuates glomerular oxidant injuries, including those in experimental nephrosis. The present study investigates the cellular mechanism of the MP-induced activation of antioxidant enzymes and their contri...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.25
更新日期:1994-01-01 00:00:00
abstract:BACKGROUND:Various gene transfer vectors as well as delivery systems have been developed; however, many problems remain to be solved. We already achieved a technique to introduce genes into glomerular mesangial cells by hemagglutinating virus of Japan (HVJ) liposome-mediated gene transfer via renal artery. The main lim...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590041390.x
更新日期:2001-04-01 00:00:00
abstract::Protein misfolding in the endoplasmic reticulum (ER) leads to ER stress. The unfolded protein response and ER-associated degradation (ERAD) interact in a coordinated manner with the ubiquitin-proteasome system and autophagy to alleviate protein misfolding or its consequences. The intersecting actions of these processe...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2012.390
更新日期:2013-07-01 00:00:00
abstract::Studies were performed in anesthetized dogs (N = 7) to determine the effects of synthetic atrial natriuretic peptide (ANP) on sodium excretion in the presence and absence of control of glomerular filtration rate produced by suprarenal aortic clamping. Intrarenal infusion of synthetic atrial natriuretic peptide (0.3 mi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.144
更新日期:1986-07-01 00:00:00