Abstract:
BACKGROUND:In interstitial fibrosis, monocytes and myofibroblasts have been directly implicated in scarring, apoptosis, and tissue necrosis. While much has been done to explore the role of these cell types individually in fibrosis, the interactive dependency of monocytes and myofibroblasts has been only marginally explored. METHODS:Alport mice were treated or not with a soluble receptor inhibitor for transforming growth factor-beta 1 (TGF-beta 1), which was previously shown to inhibit the accumulation of myofibroblasts, but not monocytes, in the tubulointerstitium. Kidneys were examined for fibrosis using several matrix markers, TGF-beta 1 mRNA expression by in situ hybridization, apoptosis using the terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL) assay, expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPS) by dual immunofluorescence microscopy, MMP activity by gelatin and in situ zymography, MMP mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR), and basement membrane degradation by dual immunofluorescence confocal microscopy and electron microscopy. RESULTS:Treated mice showed a markedly reduced accumulation of matrix proteins. Tissue monocytes express TGF-beta 1 mRNA, and TGF-beta 1 is required for myofibroblast accumulation. The number of apoptotic cells was not influenced by TGF-beta 1 inhibition. Monocytes express MMP-2, MMP-9, TIMP-2, and TIMP-3. MMP activity and mRNA expression is equally up regulated in treated and untreated Alport mice. Tubular basement membranes (TBM) around clusters of monocytes are notably degraded. TGF-beta 1 inhibition does not extend the life of Alport mice. CONCLUSION:These studies demonstrate that monocytes may influence myofibroblast accumulation via TGF-beta1, and that monocytes, and not myofibroblasts, are associated with tubular atrophy in Alport mice. Elevated MMP expression and activity is associated with TBM destruction near monocytes clusters, suggesting an anoikis mechanism may contribute to apoptosis in this model.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Rodgers KD,Rao V,Meehan DT,Fager N,Gotwals P,Ryan ST,Koteliansky V,Nemori R,Cosgrove Ddoi
10.1046/j.1523-1755.2003.00871.xsubject
Has Abstractpub_date
2003-04-01 00:00:00pages
1338-55issue
4eissn
0085-2538issn
1523-1755pii
S0085-2538(15)49012-Xjournal_volume
63pub_type
杂志文章abstract::The kallikrein-kininogen-kinin system (KKK) has been implicated in the renal sodium excretion response to changes in dietary sodium. However, both increases and decreases in the activity of this system have been observed when urinary sodium excretion is augmented by a variety of maneuvers. To further evaluate the pote...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1987.74
更新日期:1987-03-01 00:00:00
abstract::Transplanted organs express allogeneic epitopes against which a recipient's immune system mounts a destructive response. In the absence of a reliable strategy for induction of donor-specific tolerance, therapeutic immunosuppression remains the best prospect to prevent rejection, but exposes recipients to increased ris...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.268
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:Normal human podocytes are terminally differentiated and quiescent cells. It is not known why podocytes fail to proliferate in response to most forms of injury. Proliferation is regulated by cell cycle proteins and their inhibitors. The Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors (p21, p27, p5...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00213.x
更新日期:2000-08-01 00:00:00
abstract:BACKGROUND:Immune response to oxidized low-density lipoprotein (oxLDL) may modulate the process of atherogenesis and cardiovascular disease. METHODS:We performed a prospective, observational cohort study in 249 patients with end-stage renal disease (ESRD) to examine whether the serum titer of anti-oxLDL antibody can p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00692.x
更新日期:2002-12-01 00:00:00
abstract:BACKGROUND:Mast cells are growth factor-rich, bone marrow-derived cells that infiltrate injured tissue where they have been implicated in the pathogenesis of progressive fibrosis. METHODS:Mast cell infiltration and the expression of related chemoattractants was examined following 5/6 nephrectomy, a model of progressiv...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00183.x
更新日期:2003-09-01 00:00:00
abstract:UNLABELLED:Inhibition of pressure natriuresis in mice lacking the AT2 receptor. BACKGROUND:Angiotensin II type 2 (AT2) receptor knockout mice have higher blood pressures than wild-type mice; however, the hypertension is imperfectly defined. We tested the hypothesis that renal mechanisms could be contributory. METHODS...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00820.x
更新日期:2000-01-01 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::We examined the circulating levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 alpha, IL-6, granulocyte macrophage-colony stimulating factor (GM-CSF), and the anti-inflammatory cytokine IL-10, and their expression in kidneys acutely infected with murine malaria parasite...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.1998.00848.x
更新日期:1998-04-01 00:00:00
abstract::Horvat and coauthors report on trends in living kidney transplantation in 69 countries, having assembled the data from registries, national societies, the medical literature, and direct contact with transplant centers. Assembling worldwide data on live-donor kidney transplants is a commendable accomplishment that serv...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2009.23
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:Decreased red blood cell survival contributes to the anemia of chronic renal failure patients. Because patients on chronic dialysis therapy are frequently exposed to excessive complement activation, we investigated the susceptibility of this patient population to erythrocyte C5b-9 deposition, complement-medi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00277.x
更新日期:1999-02-01 00:00:00
abstract::The improvement in the anemia in patients with end-stage renal disease (ESRD) on continuous ambulatory peritoneal dialysis (CAPD) suggests that dialyzable substances present in the sera of uremic patients either inhibit erythropoiesis directly or inactivate erythropoietin (EPO). In the present study predialysis sera f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.88
更新日期:1991-04-01 00:00:00
abstract::Primary distal renal tubular acidosis is a rare genetic disease. Mutations in SLC4A1, ATP6V0A4, and ATP6V1B1 genes have been described as the cause of the disease, transmitted as either an autosomal dominant or recessive trait. Particular clinical features, such as sensorineural hearing loss, have been mainly describe...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.12.017
更新日期:2017-05-01 00:00:00
abstract::Nephrin is a slit diaphragm protein critical for structural and functional integrity of visceral glomerular epithelial cells (podocytes) and is known to be tyrosine phosphorylated by Src family kinases. We studied the role of phosphoinositide 3-kinase (PI3K), activated via the phosphorylation of nephrin, in actin cyto...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002691
更新日期:2008-03-01 00:00:00
abstract::Clinical studies have demonstrated a poor correlation between localization tests, which are designed to determine the site of urinary tract infection, and symptoms of upper urinary tract infection. One explanation is that microorganisms may be present in the kidney but not initiate an inflammatory response with associ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.200
更新日期:1992-05-01 00:00:00
abstract:BACKGROUND:Optimal nutrient intake is important in the maintenance of a positive nitrogen balance in hemodialysis (HD) patients. The objectives of this study were (1) to assess the influence of two levels of protein intakes on nitrogen balance in stable adult HD patients, and (2) to identify a minimum level of protein ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00171.x
更新日期:2000-07-01 00:00:00
abstract::Development of physiologically relevant cellular models with strong translatability to human pathophysiology is critical for identification and validation of novel therapeutic targets. Herein we describe a detailed protocol for generation of an advanced 3-dimensional kidney cellular model using induced pluripotent ste...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.05.003
更新日期:2018-12-01 00:00:00
abstract::The role of peritoneal dialysis (PD) in renal replacement therapy (RRT) remains unclear. There are no controlled trials to provide hard evidence of its efficacy. Comparative studies with haemodialysis from different centres and countries have given conflicting results even when allowing for case mix. Data from the Uni...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1046/j.1523-1755.1998.00183.x
更新日期:1998-12-01 00:00:00
abstract::Dialysis patients have a high risk of cardiovascular disease. Cardiac rehabilitation is recommended in the general population as a standard component of care and covered by Medicare for those who have undergone coronary artery bypass grafting (CABG). Here we determined the impact of cardiac rehabilitation on Medicare ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.381
更新日期:2008-10-01 00:00:00
abstract::Autosomal dominant polycystic kidney disease (ADPKD) is a renal hereditary disorder associated with increased cardiovascular mortality, due to mutations in polycystin-1 and polycystin-2 genes. Endothelial polycystin-deficient cells have an altered mechanosensitivity to fluid shear stress and subsequent deficit in calc...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.241
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:In a prior study the 21-aminosteroid (lazaroid) U74389F provided in vivo protection from oxidative stress when used as a preventive therapy in ischemia-reperfusion injury in the kidney. As the cell membrane is the principal site for lipoperoxidation, in the current study the very lipophilic 2-methylaminochro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00072.x
更新日期:1998-09-01 00:00:00
abstract::Autophagy is upregulated during ischemia-reperfusion (IR)-induced and cisplatin-induced acute kidney injury (AKI). Proximal tubule-specific Atg7 knockout mice exhibited increased renal injury compared with wild-type mice following cisplatin- and IR-induced AKI. Inhibition of autophagy by chloroquine aggravated AKI, wh...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2012.337
更新日期:2012-12-01 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:BACKGROUND:The renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta HSD2) enzyme inactivates 11-hydroxy steroids in the kidney, thereby protecting the nonselective mineralocorticoid (MR) receptor from occupation by glucocorticoids. Loss-of-function mutations in the gene encoding 11beta HSD2 (HSD11B2) result in over...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.67119.x
更新日期:2005-02-01 00:00:00
abstract::Swelling activated anion channels have recently been recognized to play an important role in not only volume regulatory electrolyte movement, but also in organic osmolyte transport. A swelling-activated, outwardly rectifying anion channel termed VSOAC (volume-sensitive organic osmolyte/anion channel) is a major pathwa...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1996.250
更新日期:1996-06-01 00:00:00
abstract::Vitamin D hydroxylated at carbon 25 (25(OH)D) is generally recognized as a precursor of active vitamin D. Despite its low affinity for the vitamin D receptor (VDR), both deficient and excessive 25(OH)D levels are associated with poor clinical outcomes. Here we studied direct effects of 25(OH)D3 on the kidney using 25(...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.210
更新日期:2015-11-01 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::Donor pretreatment of 100 mg/kg each of cyclophosphamide (CY) and methylprednisolone (P) infused 5 hours before nephrectomy invariably prolongs the survival of DLA mismatched, MLC incompatible nonlittermate Beagle renal allografts as well as the survival of mongrel renal allografts. The effect of donor pretreatment ap...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.25
更新日期:1982-02-01 00:00:00
abstract::The effects of chronic respiratory alkalosis on divalent ion homeostasis have not been reported in any species. We studied four normal male subjects during a four-day control period (residence at 500 m), during six days of chronic respiratory alkalosis induced by hypobaric hypoxia (residence at 3450 m), followed by a ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.340
更新日期:1992-09-01 00:00:00
abstract::Protein and mRNA expression of TGF-beta isoforms, TGF-beta 1, -beta 2 and -beta 3, and deposition of fibronectin containing extra domain A (fibronectin EDA+) and plasminogen activator inhibitor-1 (PAI-1) were studied in human chronic glomerulonephritis and diabetic nephropathy. Normal kidneys showed similar, weak immu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.65
更新日期:1996-02-01 00:00:00
abstract::Mesangial cells are known to secrete metalloproteinases that are capable of degrading the constituents of the GBM, and hence are potentially involved not only in the regular maintenance of the ECM components in the glomerulus, but also of contributing to any damage to these components that occurs in disease states. In...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.345
更新日期:1994-09-01 00:00:00