Abstract:
:Alterations in myocardial wall texture stand out among ADPKD cardiovascular manifestations in hypertensive and normotensive patients. To elucidate their pathogenesis, we analyzed the cardiac phenotype in Pkd1(cond/cond)Nestin(cre) (CYG+) cystic mice exposed to increased blood pressure, at 5 to 6 and 20 to 24 weeks of age, and Pkd1(+/-) (HTG+) noncystic mice at 5-6 and 10-13 weeks. Echocardiographic analyses revealed decreased myocardial deformation and systolic function in CYG+ and HTG+ mice, as well as diastolic dysfunction in older CYG+ mice, compared to their Pkd1(cond/cond) and Pkd1(+/+) controls. Hearts from CYG+ and HTG+ mice presented reduced polycystin-1 expression, increased apoptosis, and mild fibrosis. Since galectin-3 has been associated with heart dysfunction, we studied it as a potential modifier of the ADPKD cardiac phenotype. Double-mutant Pkd1(cond/cond):Nestin(cre);Lgals3(-/-) (CYG-) and Pkd1(+/-);Lgals3(-/-) (HTG-) mice displayed improved cardiac deformability and systolic parameters compared to single-mutants, not differing from the controls. CYG- and HTG- showed decreased apoptosis and fibrosis. Analysis of a severe cystic model (Pkd1(V/V); VVG+) showed that Pkd1(V/V);Lgals3(-/-) (VVG-) mice have longer survival, decreased cardiac apoptosis and improved heart function compared to VVG+. CYG- and VVG- animals showed no difference in renal cystic burden compared to CYG+ and VVG+ mice. Thus, myocardial dysfunction occurs in different Pkd1-deficient models and suppression of galectin-3 expression rescues this phenotype.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Balbo BE,Amaral AG,Fonseca JM,de Castro I,Salemi VM,Souza LE,Dos Santos F,Irigoyen MC,Qian F,Chammas R,Onuchic LFdoi
10.1016/j.kint.2016.04.028subject
Has Abstractpub_date
2016-09-01 00:00:00pages
580-97issue
3eissn
0085-2538issn
1523-1755pii
S0085-2538(16)30213-7journal_volume
90pub_type
杂志文章abstract::Space medicine and new technology such as magnetic resonance imaging of tissue sodium stores (23NaMRI) have changed our understanding of human sodium homeostasis and pathophysiology. It has become evident that body sodium comprises 3 main components. Two compartments have been traditionally recognized, namely one that...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2018.09.024
更新日期:2019-02-01 00:00:00
abstract::Metabolic acidosis is common in patients with chronic kidney disease, which is known to affect bone metabolism. We examined the effect of metabolic acidosis on the development of vascular and other soft-tissue calcifications in uremic rats treated with calcitriol. Extraskeletal calcification was measured in vivo, in c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002646
更新日期:2008-02-01 00:00:00
abstract::Although the pathogenesis of steroid-sensitive nephrotic syndrome (SSNS) remains elusive, multiple epidemiologic, clinical, and experimental studies converge on the common theme of immune dysregulation. Initially, T-cell adaptive immunity was solely emphasized; however, the role of humoral immunity in nephrotic syndro...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2019.05.031
更新日期:2019-10-01 00:00:00
abstract::Dysregulated production of adipocytokines may be involved in the development of atherosclerotic cardiovascular disease in metabolic syndrome and chronic kidney disease (CKD) associated with metabolic syndrome. The aim of this study was to determine the effects of treatment with angiotensin II (Ang II) type-1 receptor ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001810
更新日期:2006-11-01 00:00:00
abstract::Neutrophil gelatinase-associated lipocalin (Ngal, 24p3, SIP24, lipocalin 2, or siderocalin) was originally purified from neutrophils, but with unknown function. Recently, it was identified that Ngal activates nephron formation in the embryonic kidney, is rapidly and massively induced in renal failure and possesses kid...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002165
更新日期:2007-05-01 00:00:00
abstract::Changes in macula densa intracellular pH (pHi) were used to monitor the direction of flux mediated by the apical Na:2Cl:K cotransporter. At the macula densa, a decrease in luminal [Cl] ([Cl]1) from 60 to 1 mM produced cellular alkalinization secondary to a cascade of events involving a decrease in apical Na:2Cl:K cotr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.115
更新日期:1995-03-01 00:00:00
abstract:BACKGROUND:Adiponectin is an adipocyte-derived cytokine that has anti-inflammatory properties. A preliminary proteomic evaluation of urine for biomarkers of systemic lupus erythematosus (SLE) nephritis demonstrated high levels of adiponectin in SLE urine. This prompted investigation of adiponectin expression in human S...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00601.x
更新日期:2005-10-01 00:00:00
abstract::Osteonectin (SPARC, culture shock protein, BM-40) is a widely distributed glycoprotein which binds calcium and several extracellular matrix proteins, including interstitial collagens and thrombospondin, but whose physiologic role remains undefined. In the present studies, we have demonstrated that immunoreactive osteo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.8
更新日期:1992-01-01 00:00:00
abstract::This very brief summary of the various possible contributions of PG to normal and abnormal renal function should highlight the problem of assigning a specific role to PG in overall renal physiology and pathophysiology. PG produced in specific segments of the nephron will affect specific functions occurring in this seg...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1986.13
更新日期:1986-01-01 00:00:00
abstract::In Australia, Canada, New Zealand, and the United States indigenous people have high rates of chronic kidney disease but poor access to effective therapies. To more fully define these issues, we compared the demographics of renal transplantation of indigenous patients in these 4 countries. Data encompassing 312,507 in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.236
更新日期:2009-09-01 00:00:00
abstract::To date direct evidence for the presence of a H-K-ATPase in the medulla comes from proton and potassium transport studies performed on K-restricted animals and K dependent ATP hydrolysis and Rb uptake in both normal and K-depleted animals. The present work examines K-dependent acidification in the medulla of rabbits o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.392
更新日期:1992-11-01 00:00:00
abstract:BACKGROUND:Vascular endothelial growth factor (VEGF) and its receptors have been implicated in the pathogenesis of diabetic nephropathy. The objective of this study was to determine whether alterations of the plasma and urinary VEGF and sFLT-1 levels were related to the stages and risk factors of diabetic nephropathy. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00067.x
更新日期:2005-01-01 00:00:00
abstract::Murine double minute (MDM)-2, an E3 ubiquitin ligase, promotes cancer cell survival and growth, by degrading the cell cycle regulator p53. Antagonism of MDM2 by the small-molecule cis-imidazoline nutlin analogs is under current study for cancer therapy. To test whether MDM2 also promotes regenerative cell growth, we d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.482
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:The relationship between blood pressure (BP) and mortality in hemodialysis patients has remained controversial. Some studies suggested that a lower pre- or postdialysis BP was associated with excess mortality, while others showed poorer outcome in patients with uncontrolled hypertension. We conducted a multi...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1523-1755.2004.00812.x
更新日期:2004-09-01 00:00:00
abstract::Hypoxia in the embryo is a frequent cause of intra-uterine growth retardation, low birth weight, and multiple organ defects. In the kidney, this can lead to low nephron endowment, predisposing to chronic kidney disease and arterial hypertension. A key component in cellular adaptation to hypoxia is the hypoxia-inducibl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.06.015
更新日期:2017-12-01 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: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:BACKGROUND:This study evaluated the effects of dietary sodium manipulation in dogs on the regulation of canine angiotensin receptors (cAT1 and cAT2) in the kidney and adrenal. METHODS:Isolated glomeruli and membranes from renal medulla and the adrenal gland were used in radioligand binding assays from two groups of do...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590051881.x
更新日期:2001-05-01 00:00:00
abstract::[Arg(8)]-vasopressin (AVP) has several functions via its three distinct receptors, V1a, V1b, and V2. The V1a vasopressin receptor (V1aR) is expressed in blood vessels and involved in vascular contraction. Recently, we generated V1a receptor-deficient (V1aR(-/-)) mice and found that they were hypotensive. In addition, ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2009.319
更新日期:2009-11-01 00:00:00
abstract:UNLABELLED:Expression of apoptosis regulatory genes in chronic cyclosporine nephrotoxicity favors apoptosis. BACKGROUND:Chronic cyclosporine (CsA) nephrotoxicity is characterized by interstitial fibrosis, tubular dropout, and loss of cellularity in areas of fibrosis. Apoptosis was found to play a role in CsA-induced f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00794.x
更新日期:1999-12-01 00:00:00
abstract::In rodents, mercuric chloride (HgCl2) causes an autoimmune disorder with glomerulonephritis (GN), and represents an animal model for the pathogenesis of GN. We have tested the hypothesis that HgCl2 induces major histocompatibility complex (MHC) expression in renal parenchymal cells, and studied the kinetics of this in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.33
更新日期:1991-02-01 00:00:00
abstract:BACKGROUND:The characteristic feature of Goodpasture disease is the occurrence of an autoantibody response to the noncollagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] in the alveolar and glomerular basement membrane. These antibodies are associated with the development of a rapidly progressive ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.055003936.x
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND:Epidermal growth factor (EGF) plays an important role in renal tubular regeneration after ischemic injury in kidney. The present study reports the association between the renin-angiotensin system (RAS) and EGF, and the effect of angiotensin II blockade with losartan (LSRT) on EGF expression in an experimenta...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.060003847.x
更新日期:2001-09-01 00:00:00
abstract::Pathogenesis of vascular calcification in chronic kidney disease. Background. Hyperphosphatemia and hypercalcemia are independent risk factors for higher incidence of cardiovascular events in patients with chronic kidney disease. In addition to increased calcium-phosphate product, hyperphosphatemia accelerates the pro...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1111/j.1523-1755.2005.00421.x
更新日期:2005-08-01 00:00:00
abstract::We investigated the effects of epidermal growth factor (EGF) and arginine vasopressin (AVP) on Raf-1-MAP kinase cascade, including Raf-1-kinase (Raf-1-K), MAP kinase kinase (MAPKK), MAP kinase (MAPK) and S6 kinase (S6K) in Madin-Darby canine kidney (MDCK) cells. In a dose-dependent manner (10(-10) M to 10(-6) M), EGF ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.346
更新日期:1995-09-01 00:00:00
abstract::The present studies address the metabolic processes that support the reabsorption of sodium and the secretion of bicarbonate in the interspersed but distinct principal and intercalated cells of the cortical collecting duct (CCD). In microperfused rabbit CCD, sodium reabsorption was measured by lumen-to-bath 22Na flux,...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00754.x
更新日期:1998-02-01 00:00:00
abstract::Proteomics-based assays have substantially improved diagnostic accuracy in systemic amyloidosis and have led to the discovery of novel amyloidogenic proteins. The observation that human apolipoproteins are increasingly represented is intriguing and highlights the complex, and partially known, mutual effects of the mis...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.05.029
更新日期:2016-09-01 00:00:00
abstract::Twelve patients with progressive renal failure were placed on a very low protein diet supplemented by an essential amino acid-keto acid mixture for six to twelve months. Total daily intake was 0.04 g nitrogen/kg and 50 kcal/kg. Eight subjects had a significant change in the slope of reciprocal plasma creatinine, becom...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.99
更新日期:1986-05-01 00:00:00
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,...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2000.00362.x
更新日期:2000-11-01 00:00:00
abstract::Acute kidney injury (AKI) increases the risk for chronic kidney disease (CKD). However, there are few tools to detect microstructural changes after AKI. Here, cationic ferritin-enhanced magnetic resonance imaging (CFE-MRI) was applied to examine the heterogeneity of kidney pathology in the transition from AKI to CKD. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.08.021
更新日期:2021-01-01 00:00:00